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<p>Z5091101: /* History */</p> <hr /> <div>=The Contribution of Neural Crest Cells to the Adrenal Medulla=<br /> ----<br /> {{2018ANAT2341ProjectHeader}}<br /> <br /> <br /> ===Introduction===<br /> <br /> ----<br /> <br /> The neural crest of an embryo migrates and differentiates to form various components of the body. This transient population of pluripotent stem-cells give rise to many complex and different structures across the adult by chemical signalling. One of these tissues is the medulla of the adrenal gland which is involved in the production of epinephrine and norepinephrine. This project will comprehensively outline the history of neural crest research, the embryonic developmental time course, tissue and organ structure, molecular mechanisms, abnormalities, animal models and current research.<br /> <br /> ===History===<br /> ----<br /> '''Describing the neural crest'''<br /> [[File:Wilhelm_His_History_Wilhelm.jpeg|left|230px|thumb|Wilhelm His]]<br /> [[File:NC Location.jpg|right|450px|thumb|The neural crest]]<br /> The "neural crest" is a structure in the embryo and is the junction between the neural and epidermal ectoderm. It is exclusive to vertebrates and forms a range of structures{{#pmid:22230617|PMID22230617}}. The neural crest contributes a large number of cells of varying structure and function that directly or indirectly contribute to the development of tissues and organs within the body {{#pmid:19179766|PMID19179766}}. In 1868, the neural crest cells were first identified in a chick embryo as a collection of cells known as "Zwischenstrang" by Professor Wilhelm His {{#pmid:22820859|PMID22820859}}. Wilhelm His was among the first to provide an explanation for the mechanics governing the developing embryo as well as the physiology and the organs that the differing germinal regions would eventually give rise to {{#pmid:19179766|PMID19179766}}. This was due to his work in creating one of the first microtomes, a device that enables thin slicing of tissue, which enabled him to see embryonic tissues at greater magnifications and resolutions. He gave the neural crest the name, the ganglionic crest {{#pmid:26970616|PMID26970616}}. In 1878, the term neural ridge was used to describe this collection of cells but the term neural crest was later coined by Arthur Milnes Marshall in 1879 in a paper he worked on disseminating the knowledge from his research on the development of cranial nerves in chicken embryos. {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1890s-1950s'''<br /> The neural crest is the point of origin for spinal/cranial ganglia and neurons. This theory received little criticism and was not contested much by other researchers prior to the 1890s. This is owing to the fact that the neural crest is quite closely related to the neural tube and thus this relationship makes sense. This discovery was made by His and Marshall, however, they found this out independently of one another.In the 1890s, Julia Platt, claimed that odontoblasts as well as the cartilages forming the facial and pharyngeal arch skeletons came from the ectoderm. This created much debate and was contested by many{{#pmid:22820859|PMID22820859}}. <br /> <br /> This is because this theory completely contradicted the germ-layer theory, whereby skeletal tissues originate at the mesoderm and not the ectoderm. The controversies this finding created brought about a slowing down of research, as demonstrated by a gap of almost 40 years between the theory that skeletal tissues originating from the neural crest. Today, it is known that the neural crest does indeed play a role in the development of the skeleton in vertebrates, particularly, the cranial neural crest. Although these studies were occurring, the focus was still primarily on researching pigment cells and ganglia of the spine up until the 1950s, when Sven Hörstadius' major work on the neural crest was published, titled "The Neural Crest: Its properties and derivatives in the light of experimental research". This work focused on experimental data tracing the development of the cartilaginous skeleton derived from the neural crest {{#pmid:19179766|PMID19179766}}.<br /> <br /> This period from the 1890s to the 1950s was a time of emerging research and experimentation, with various contributions of the neural crest being studied. This was done through a range of experiments involving removal of parts of the neural crest to examine the effects on development of birds and amphibians as well as transplantation of parts of neural crest to enable an understanding of patterns of cell migration {{#pmid:26970616|PMID26970616}}.<br /> <br /> '''1960s - 1970s'''<br /> In the 1960s, the migration patterns of neural crest cells were studied in avian embryos (birds). This was done through new techniques involving marking the cells with radioactive substances such as 3H-thymidine {{#pmid:26970616|PMID26970616}}. This was a shift from studying the embryos of amphibians. This was inspired by studies conducted in the 1960s on neural crest cells migrating from the brain and spinal cord, known as trunk and cranial neural crest cells {{#pmid:19179766|PMID19179766}}. The cranial neural crest eventually becomes the bones, cartilage and connective tissues forming the foundation of the face, ears and teeth. The trunk neural crest cells can either become melanocytes or can migrate into sclerotomes which are later contributors to the cartilage of the spine and the dorsal root ganglia {{#pmid:22820859|PMID22820859}}. The cells in the trunk neural crest that migrate vertically become the sympathetic ganglia, the nerves proximal to the aorta and the adrenal medulla <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. In the 1970s many detailed maps signifying the pathways of many of the neural crest cells appeared as well as an understanding that the environment in which the neural crest cells are found plays a major role in their final development as well as the occurrences of abnormalities in the fetus {{#pmid:19179766|PMID19179766}}.<br /> <br /> <br /> '''1980s - 21st century'''<br /> [[File:Regions_of_NC_Cells.jpg|left|Neural crest regions|thumb|465px]]<br /> From the 1980s-1990s, the causative agent of organ transformation from one to another (homeotic patterning), as well as the Hox genes which regulate the axis of most symmetrical animal embryos were founded and studied. The neural crest, which previously was divided into the cranial and trunk regions, was now further divided into the vagal and sacral neural crest, the cardiac neural crest and the cephalic neural crest {{#pmid:19179766|PMID19179766}}. The vagal & sacral neural crest gives rise to the parasympathetic ganglia found in the gut. Without these ganglia, peristalsis, is not possible <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. The cardiac neural crest contributes to the valves, septa and major blood vessels of the heart, as well as connective tissues and cartilage{{#pmid:19179766|PMID19179766}}. This is important for the structure of the heart as well as its overall function, enabling it to move blood around the body efficiently as well as keep pulmonary and aortic circulation separated <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> <br /> In the mid 1980s, the first studies bringing about some information on the destination of ventrally migrating neural crest cells were conducted using the antibody HNK-1, as it is known to detect antigens on neuroectodermal cells & label the migratory cells. Where previously it was thought that trunk neural crest cells migrated whilst avoiding the somites, these studies showed that the trunk neural crest cells migrated through the rostral half of each somite. How this worked was eventually understood as a result of chemotactic factors that attract and repel the cells to follow this migration {{#pmid:26970616|PMID26970616}}.<br /> <br /> <br /> Today, knowledge of the neural crest cells, their migration patterns, modes of differentiation, derivatives and apoptosis (cell death) are being studied extensively. This is being done on a comparative basis between different organisms, to add further evidence for evolution {{#pmid:19179766|PMID19179766}}. The neural crest is definitely forging a "crest" between the fields of developmental and evolutionary biology, as it is a structure '''shared exclusively by all vertebrates'''. Invertebrates do not derive their specialised cells from the neural crest as they do not have one, rather, they derive these from the endomesoderm {{#pmid:22230617|PMID22230617}}.<br /> <br /> <br /> '''Future directions'''<br /> <br /> Since its discovery by His, the neural crest field has made great progress, from studies performed on the structure, to analysis of the molecules and whether certain aspects of the neural crest are specific to a single species of organism, or to all vertebrates collectively. Future work on the cranial neural crest needs to be done as well as identifying and categorising the networks responsible for the proliferation and death of cells, as well as how the cells move and migrate, as well as the gene regulatory networks (GRNs) that regulate the synthesis of proteins {{#pmid:22230617|PMID22230617}}.<br /> . Advances in technology will undeniably lead us to more answers on the subject and studies that include imaging, mathematical and molecular modelling will greatly enhance our growing understanding of how neural crest cells move {{#pmid:26970616|PMID26970616}}.<br /> <br /> ===Developmental time course===<br /> ---- <br /> <br /> [[File:Adrenal_Medulla_Developmental_Timeline.jpg|right|thumb|500px]]<br /> <br /> The adrenal gland has two distinct sections, the cortex and the medulla, both with different embryonic origins. The cortex accounts for 90% of the adrenal glands and arises from intermediate mesoderm. The medulla only accounts for 10% of the adult adrenal glands, however it has neural crest embryonic origin. The medulla consists of chromaffinoblast cells which are migrant neuroblast cells from the neural crest, therefore the adrenal medulla is a component of the sympathetic nervous system.{{#pmid:21175739|PMID21175739}} Neural crest cells replicate in week 7 and begin to differentiate in week 8, the cells then migrate to the developing adrenal gland in week 9 of development.{{#pmid:25255746|PMID25255746}}{{#pmid:18279781|PMID18279781}} The neural crest cells infiltrate the cortex and the chromaffin cells are scattered islands in the cortex.{{#pmid:23354096|PMID23354096}} Throughout development the cells will become more compact in the centre of the gland, during this period of development the adrenal gland is growing rapidly. The gland is abnormally large until the second trimester and the medulla is much thicker prenatally.{{#pmid:18279781|PMID18279781}}{{#pmid:21175739|PMID21175739}}<br /> <br /> <br /> ===Embryonic origins===<br /> ----<br /> [[File:Trunk_NCC_migration.jpg|left|450px|thumb|Trunk NCC migration]]<br /> The adrenal gland is made up of the adrenal cortex and adrenal medulla, which both have different embryonic origins. The adrenal medulla arises from the neural crest tissue, found near the level of the coeliac plexus & sympathetic ganglion at somites 18-24 {{#pmid:16124976|PMID16124976}}. Specifically, this neural crest tissue comes from the trunk neural crest cells (see above figure to determine the approximate location in an embryo) <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> The trunk neural crest coordinates the development of the endocrine system, secretory cells, the peripheral nervous system and, to some degree, skeletal development, as well as innervation of the intestine {{#pmid: 28287247|PMID 28287247}}. The trunk neural cells arise caudally, undergo an epithelial to mesenchymal transition and follow three migratory pathways {{#pmid:20399766|PMID20399766}}.<br /> [[File:Differentiation_of_NCC.jpg|left|580px|thumb|Differentiation of chromaffin cells]]<br /> - A dorsolateral pathway (between ectoderm and somites), these become melanocytes, travel up to the point of the dermis and become a major part of the hair follicles and skin <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> - A ventrolateral pathway (through the somites)<br /> - A ventromedial pathway (between neural tube and posterior schlerotome){{#pmid:20399766|PMID20399766}}.<br /> <br /> Migration of neural crest cells from the sympathetic ganglion is what leads to the development of the adrenal medulla. In week 8 of development, immature cells called neuroblasts migrate through to the inner portion of the medulla, where they become the adrenal medulla {{#pmid:19683477|PMID19683477}}. Chromaffin cells are neuroendocrine cells and are found in the sympathetic ganglia and make up the majority of the adrenal medulla{{#pmid:19683477|PMID19683477}}. They synthesise and release a range of hormones in the body and arise from the temporary neural crest. The term chromaffin was inspired by the staining capacity of these cells when they came into contact with chrome salts. They make, store, export and use catecholamines, responsible for making noradrenaline and originate at the caudal region of somites 18-24 of the neural crest, also known as the adrenomedullary region {{#pmid:19683477|PMID19683477}}.<br /> <br /> For cells to leave the neural crest and begin their migration, certain conditions need to be met, that is, the cells need to be loosely connected, their tight junctions becoming relaxed, initiated by "Slug protein" and a loss of N-Cadherin which also leads to the loosening of these junctions. The surrounding matrix as well as chemotactic and stem cell factors of the neural tube are then what dictates how the neural crest cells move, some proteins stopping their migration to that area and others encouraging the movement <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. After splitting apart, the first neural crest cells move ventrally and pass into the spaces between the somites and then, through the anterior portions of each segment until they arrive at the para-aortic sites, where they become the cells of the sympathetic ganglia and the adrenal medulla {{#pmid:19683477|PMID19683477}}. BMP-4 (bone morphogenetic protein 4) then acts on these neural crest cells, preventing them from becoming cells that have a neural function and causing them to become chromaffin cells at the adrenal medulla. Glucocorticoids then play a role in maintenance of chromaffin cells in postnatal life, this was only found recently, as previously it was thought that glucocorticoids were responsible entirely for the differentiation of neural crest cells into chromaffin, or adrenomedullary cells {{#pmid:23220335|PMID23220335}}.<br /> <br /> ===Anatomy and Functions===<br /> <br /> ----<br /> <br /> ====Anatomy and Histology====<br /> <br /> The adrenal medulla makes up the inner section of the adrenal glands, and is surrounded by the cortex, and a connective tissue capsule. It lies in the centre of the gland and it rarely measures no more than 2mm in thickness {{#pmid:21107679|PMID21107679}}. The cells of the adrenal medulla are derived from the neural crest as opposed to the mesodermal origins of the cortex. The adrenal medulla contains secretory cells called chromaffin cells due to the agents they produce when oxidised, such as chromate {{#pmid:11215683|PMID11215683}}. These cells secrete epinephrine, norepinephrine, chromogranin and neuropeptides in response to various substances such as acetylcholine <ref name="PMID11215683"/>. [[File:ADRENAL MEDULLA .jpg|600px|thumb|right|Adrenal Medulla Histology]]<br /> <br /> There are many types of highly differentiated cells in the adult adrenal medulla: <br /> - Epinephrine cells (90% of all chromaffin cells) {{#pmid:24715564|PMID24715564}}<br /> - Norepinephrine cells (10% of all chromaffin cells) <ref name="PMID24715564"/><br /> - Small granule-containing cells (SGCs) <ref name="PMID11215683"/><br /> <br /> These cells also synthesise, store and secrete catecholamines through controlled and regulated pathways <ref name="PMID24715564"/>, such as various peptides like substance P and neurotensin.These cells have unique neuroendocrine characteristics as a result of their neural-crest origin. They receive preganglionic innervation by thoracic splanchnic nerves, and could almost be considered a specialised sympathetic ganglion. With postganglgionic bodies, cells of the medulla are densely clustered around their vasculature for the secretion of hormones into the bloodstream to moderate the concentration of epinephrine and norepinephrine. The adrenal medulla also contains presynaptic sympathetic ganglion cells <ref name="PMID11215683"/>. The small granule-containing cells are usually found in clusters whereas, the ganglion cells are found either individually or in clusters, usually dispersed among the chromaffin cells or among the nerve fibres {{#pmid:18021328|PMID18021328}}. During embryonic development (around weeks 9-12), in contrast to the developing adrenal cortex, the medulla does not show evidence of an organised structure other than a small cluster of cells scattered throughout its cortex {{#pmid:30247985|PMID30247985}}. <br /> <br /> <br /> <br /> ====Related Anatomy====<br /> <br /> The tissue and organ structure of the adrenal medulla should be understood with regard to its specialised function within the sympathetic nervous system. <br /> <br /> The medullary region of the adrenal glands is tasked with the endocrine secretions of epinephrine and norepinephrine in response to environmental stressors that are signalled for by the sympathetic nervous system. That is, the secretion of fight-or-flight response hormones in order to restrict vasculature to the trunk and increase vascular activity in the peripheral musculature.<br /> <br /> The adrenal glands and its medulla are supplied by several branches of the great vessels in the abdominal cavity. The secreted catecholamines in the medulla are directly able to pass to the blood stream this way with a rich surface area.<br /> <br /> The adrenal glands and their contents are retroperitoneal in the adult and varied in shape, with the left often being semilunar and right being pyramidal. Nervous supply of the adrenal glands is achieved by contributions from the splanchnic nerves of the celiac plexus. {{#pmid:11215683|PMID11215683}} <br /> <br /> [[File:Dd.jpg|400px|thumb|right|Adult Adrenal Glands in situ]] <br /> ----<br /> <br /> ====Role of the Adrenal Medulla====<br /> <br /> Understanding the biochemistry of catecholamines is necessary to see how the adrenal medulla is designed in the stages of embryology and how it is suited for life in the neonate and adult. <br /> <br /> The epinephrine and norepinephrine in the neonate and adult work by primarily changing the osmoregulatory state of vasculature in organs. With the exclusion of their neuromodulatory and neurotransmitter functions, epinephrine and norepinephrine are mainly tasked with the control of sympathetic and parasympathetic supplies. <br /> <br /> Norepinephrine is a constrictor of peripheral vasculature by antagonising the action of surface receptors expressed on the endothelium of blood vessels, specifically Alpha-1 and Alpha-2 receptors, such that vascular resistance increases. <br /> <br /> Epinephrine is both a vasoconstrictor and vasodilator, depending on what receptors it attaches to. As a non-selective adrenergic agonist, it acts on Alpha-1, Alpha-2, Beta-1, Beta-2 and Beta-3 receptors that are found throughout the body's tissues, yielding many different physiological responses. {{#pmid:19396395|PMID19396395}}<br /> <br /> '''Adult Function'''<br /> <br /> While the adrenal cortex releases glucocorticoids in response to long term stress, the adrenal medulla releases its hormones in response to short-term, acute stress. The adrenal medulla contains the neuroendocrine chromaffin cells which are responsible for secreting adrenaline and noradrenaline. The function of these hormones is primarily to maintain the body’s homeostasis, especially of the internal organs, and to properly activate the autonomic stress response, more commonly known as the ‘fight or flight’ response {{#pmid:30237243|PMID30237243}}. Thus the function of the medulla includes signalling the liver and skeletal muscles to convert glycogen into glucose for increased energy. This results in increased blood glucose levels. These hormones also increase the heart rate, pulse and blood pressure in preparation for the fight or flight response. In addition to this, these hormones dilate the lung airways and prompt vasodilation to further increase oxygenation of important organs such as the lung, brain and heart. Vasoconstriction of blood vessels is also prompted to other less essential organs such as the bladder and the digestive system.<br /> <br /> Other effects also include pupil dilation, dry mouth and a loss in peripheral vision <ref name="PMID18021328"/>. Paramount to the correct response of chromaffin cells is the synaptic connection of the preganglionic cells which originate from the central nervous system and project axons into the adrenal medulla. While this is a very important relationship, the mechanisms of this remains unknown <ref name="PMID30237243"/>. In addition to the release of catecholamines, cells in the medulla also release peptides through the process of exocytosis from chromaffin granules, to help regulate blood pressure and regulation throughout the body. These peptides also regulate the release of adrenaline and noradrenaline, blood vessel contraction and the immune response <ref name="PMID18021328"/>. <br /> <br /> '''Embryonic function'''<br /> <br /> The current knowledge about the development of the adrenal gland is limited, with nearly all models being from animals, and very limited functional data available from human fetal adrenals <ref name="PMID30247985"/>. Thus for these reasons, there is scarce information available on the embryonic adrenal medullary functions. Nevertheless, there is accumulating evidence that the catecholamines in the fetal adrenal medulla plays an important role in the time of delivery by controlling thermogenesis and heart regulation {{#pmid:6998630|PMID6998630}}. <br /> <br /> The hormones released by the medulla during birth also play a key role for the newborn’s adaptation to extrauterine life. Despite the immaturity of the adrenal medulla at birth, it is known that respiratory, metabolic and cardiovascular changes during delivery are dependent on the adrenomedullary hormones {{#pmid:3280659|PMID3280659}}. Experimental data from human and animal fetal research shows that the fetal sympathoadrenal system, consisting of the adrenal medulla, sympathetic neurons and chromaffin tissue work together to maintain fetal homeostasis {{#pmid:6346884|PMID6346884}}. The adrenal medulla thus appears to provide vital physiological functions for fetal and neonatal survival, especially during birth. <br /> <br /> <br /> ----<br /> <br /> ===Molecular mechanisms/factors/genes===<br /> ----<br /> <br /> ====Genes and Transcription Factors Involved with the Adrenal Medulla's Development====<br /> <br /> The 'story' of the Adrenal Medulla's neural crest tissue begins at the process of neurulation, the formation of the neural tube from the folding neural plate, which is comprised of developing ectoderm which is opposite to the primitive streak. It is here that several key chemical players are at work. The classic interpretation of Sonic Hedgehog (Shh) and Wnt signalling pathways as the only mediators here, has been shown to be incorrect. Research has uncovered other signallers such as: <br /> <br /> *Bone-Morphogenic-Protein-4 (BMP4) for the regional expression of nervous system distinctions in the growing neural plate. This maintains two important embryonic trancription factors known as Paired-Box (PAX) Genes 3 and 7 which can allow for expression of neural crest markers HNK-1, SRY-Box (SOX) 8, 9 and 10 as the neural tube closes and the neural crest delaminates from the folding. {{#pmid:16688176|PMID16688176}} <br /> <br /> *Slug via Wnt signalling, this allows for the loosening of gap junctions in the extracellular matrix surrounding the newly-formed neural tube and trunk of the embryo. This extracellular matrix has chemo-attractant molecules<br /> <br /> [[File:Catecholamine_Synthesis.jpg|400px|thumb|right|Biochemical Cascade of Catecholamine Synthesis]]<br /> <br /> The importance of Somitogenesis and Neural Crest come to a head when neural crest cells must migrate anteriorly past somites 18 to 24, utilising chemoattraction from cells of the extracellular matrix between the neural tube and Adrenal Cortex's primordial mesoderm <br /> <br /> Members of the SOX gene family have multiple key contributors to Neural Crest in the Adrenal Medulla.<br /> <br /> Mouse models have demonstrated that SOX-10 knock-outs (mice whose DNA has been engineered to not express SOX-10) do not have an adrenal medulla. There has also been suggestion that SOX-8,9 and 10 are all strongly related to the migratory patterning of neural crest cells to the developing adrenal glands. {{#pmid:18272785|PMID18272785}}<br /> <br /> The TH gene (for Tyrosine Hydroxylase) encodes the aforementioned enzyme in the adrenal medulla and central nervous system. Tyrosine Hydroxylase is crucial in biochemical pathways and cascades for the synthesis of catecholamines and other CNS neurotransmitters. The conversion from L-Tyrosine to L-DOPA is dependent upon the catalytic action of Tyrosine Hydroxylase. From there, L-DOPA can make Dopamine and eventually Epinephrine and Norepinephrine as well. {{#pmid:19396395|PMID19396395}}<br /> <br /> ===Abnormalities/abnormal development===<br /> ----<br /> <br /> Abnormalities of the Adrenal Medulla are much less common than its mesoderm-derived shell of the Adrenal Gland. Three of the most notorious abnormalities of the Adrenal Medulla include:<br /> <br /> * Pheochromocytomas<br /> * Ganglioneuromas<br /> * Neuroblastomas<br /> <br /> <br /> Pheochromocytomas (PCCs) are variable neoplasias of the adrenal medulla's chromaffin cells. There are many classifications of PCCs, with autosomal-dominant germ-line mutations and heredities being one of the main causes. Familial pheochromocytoma-paraganglioma (PGL) syndromes exist, with PGL1 having mutations of the SDHD gene, PGL3 being mutated of the SDHC gene and PGL4 having mutation of the SDHB gene. These phenotypically present as extra-adrenal chromaffin bodies, malformation of the adrenal glands themselves, absence of chromaffin bodies and fluctuations in circulating catecholamines. {{#pmid:18021328|PMID18021328}}<br /> <br /> Ganglioneuromas (GNs) are classically-benign growths that are very rare and arise from neural crest tissue. They are not circumscribed to the adrenal medulla, but also are found in the sympathetic chain and trunk ganglia. As a result of their scarcity, not much is known about them other than a few aberrant genes and generic clinical presentations. ERBB3, the receptor tyrosine kinas is understood to be important in the development of GNs, as well as an extremely high prevalence of up-regulated GATA3. A key thing to note is also the '''lack''' of N-MYC expression in GNs, which is quite prominent in neuroblastomas and other neoplasias. {{#pmid:29085827|PMID29085827}} {{#pmid:23715162|PMID23715162}} <br /> <br /> Neuroblastomas (NBs) are a more aggressive form of cancer, derived from neuroblasts - the precursor cells to neurons. A rather common pediatric cancer, they are often in children who are in risk factor groups such as those with aforementioned familial cancer syndromes, neurofibromatosis-1. These tumours often present with extremely variable catecholamine concentrations, which has implications for blood pressure, heart contractility and much more. Urinary excretion of norepinephrine, homovanillic acid (HVA) and vanilmandelic acid (VMA) can be used to help diagnose a suspected lesion of the adrenal gland, as these chemicals are associated with altered chemical cascades that are suspicious of neuroblastic change. {{#pmid:16372223|PMID16372223}}<br /> <br /> <br /> Apart from these abnormalities, there are other pathologies that may be connected to the adrenal medulla. One such example is a pathology of the Organ of Zuckerkandl. Also known as the para-aortic body, the Organ of Zuckerkandl is a primarily-gestational organ comprised of chromaffin cells and serves a similar purpose to the adrenal medulla in neonatal life.<br /> <br /> ===Animal models===<br /> ----<br /> Animal models are an integral part of research in embryology. In particular due to the moral concerns regarding the use of humans in scientific research. As a result different animals are used as substitutes to simulate the same environments and hope to achieve results that would also be able to represent humans as well. Prenatal adrenal gland development has been described in a number of scientific reports dating from the 1900s to studies in more recent years. These involved a variety of animal models such as ox, sheep, swine and most commonly mice. <br /> <br /> ====Chromaffin cells====<br /> There has been extensive research conducted into the adrenal chromaffin cells and their embryological developments. As explained above nueral crest cells are pluripotent meaning they are able to differentiate into multiple different cells{{#pmid:19377845|PMID19377845}}. The neural crest cells give rise to chromaffin cells of the adrenal medulla.<br /> <br /> =====Rat Models=====<br /> [[File:Adrenal gland.png|300px|thumb|right|3D images showing TH - positive cells accumulating at the cranial and Caudal ends of the adrenal gland.]]<br /> Previous research has reported that nueral crest cells differentiate into chromaffin cells around 19 days of gestation before forming the adrenal medulla{{#pmid:28684471|PMID2868441}}. Past research had also suggested that neural crest derived adrenal gland cells migrate using the sympathetic ganglia to the adrenal gland or preaortic ganglion, following different pathways, to reach their specific destination. However the results have shown that the pathways used to reach its destinations overlapped. This would suggest that there is a possibility of the cells using the same pathway to move from the beginning production to the destination that is the adrenal medulla (for chromaffin cells) and the preaortic ganglion (other cells involved in the sympathetic system). <br /> <br /> One particular study done by M.Yamato in 2004, along with his fellow scientists attempted to study the migration of neural crest cells in Wistar rats. In order to observe the formation adrenal medulla from the neural crest cells during the embryonic period, Yamato used anti - tyrosine hydroxylase (TH) antiserum injected into the rat embryos between 13-17 days of gestation. The anti - TH antiserum stain allows the scientists to visualize the neural crest cells under a light microscope. Later three dimensional images were created. From the images observed between 13 to 15 days of gestation, the TH - positive cells can be seen to move from the dorsal to the adrenal primordium{{#pmid:15240937|PMID15240937}}. After 16 days it was observed that a capsule had formed in some parts and TH - positive cells had penetrated the adrenal gland{{#pmid:15240937|PMID15240937}}. At seventeen days, TH - positive cells can be seen collecting at the medial part of the adrenal gland. The reconstructed images also shows that at the later stages during the 16-17 days of gestation, the accumulation of TH - positive cells grow and in combination with cell division leads to the formation of the adrenal medulla.<br /> <br /> =====Chicken models=====<br /> Chicken and rat models are often the most commonly used models when dealing with neural crest cells. A particle review article, collates multiple researchers results and presents evidence to discuss previous information suggesting that sympathetic neurons and chromaffin cells do not share a common progenitor{{#pmid:3693940|PMID3693940}}. The relevant study involved the use of cell cultures, Sympathoadrneal (SA) progenitor cells from embryonic(from chick embryos) and eary developmental stages were able to be procured. From these cultures it was easy to identify that glucocorticoids were crucial in the differentiation of SA cells into their derivatives, sympathetic neurons and chromaffin cells.<br /> <br /> [[File:Expression of BMP protein 4 .jpg|300px|thumb|right|Shows the movement of the chromaffin progenitors moving from each stage of development. sg: sympathetic ganglia ac:adrenal cortical region ag: adrenal gland da: dorsal aortic region]]<br /> <br /> Another study conducted deals with the role of the bone morphogenetic protein(BMP-4) and its importance in the development of the adrenal medullary cells, chromaffin cells{{#pmid:18945349|PMID18945349}}. Previous research had shown that BMP - 4 a growth factor is plays an important role in the regulation of chromaffin cell production{{#pmid:10679774|PMID10679774}}. The researchers incubated chick embryos for 3 - 9 embryonic days and dissected them to be used for tissue cultures. Embryonic day 8 chick embryos had BMP - 4 overexpressing cells implanted in the sympathetic ganglia area, as well as other neurons which contained chromaffin like cells. What was observed was an increase in size and numbers of 'chromaffin' granules{{#pmid:18945349|PMID18945349}}. As a result it was concluded that although BMP - 4 promotes certain chromaffin traits, it does not have the capability to convert sympathetic neurons into a chromaffin type cell.<br /> <br /> ===Current research (labs)===<br /> ----<br /> <br /> ==== Generation of Adrenal Chromaffin-like Cells from Human Pluripotent Stem Cells====<br /> <br /> As explained above the adrenal medulla plays an important part in the autonomic system of an adult human. The chromaffin cells, in particular, are important neural crest derived cell that is closely related to the adrenal medulla. Previous findings have focused specifically on the mechanisms controlling the neural crest cell migration and how these cells go on to form the different derivatives in their particular destinations in the embryo. For example, as previously explained studies have shown that chromaffin cells have been observed to move to the adrenal gland to form the medulla of the adrenal gland. This report goes through a recent study that involves the adrenal medullary cells, in particular chromaffin cells, and their potential to be used to model certain pathological diseases related to these cells. This is part of a study that also involves neural crest cells and their ability to differentiate into multiple different types of cells<ref>Lumb, R., & Schwarz, Q. (2015). Sympathoadrenal neural crest cells: The known, unknown and forgotten?. Development, Growth & Differentiation, 57(2), 146-157. doi: 10.1111/dgd.12189</ref>. Neural crest cells and SAPs from human embryonic cells and induced pluripotent stem cells were generated to be used in the experiment. By exposing the pluripotent stem cells to BMP4 in vitro, results showed that these cells would 'upregulate' the chromaffin cell - specific marker PMNT (an enzyme that synthesizes adrenaline). Furthermore when the cells from human embryos were implanted into avian embryos, there was a visible potential for the human cells to differentiate into cells that expressed the chromaffin cell markers{{#pmid:5768882|PMID5768882}}.<br /> <br /> Link to article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768882/<br /> <br /> ====Multipotent Peripheral Glial Cells Generate Neuroendocrine Cells of the Adrenal Medulla====<br /> <br /> Similar to the first study, this one also focuses on the chromaffin cells and their relationship to the adrenal medulla. Chromaffin cells often represent the main endocrine component that is believed to differentiate from neural crest cells{{#pmid:28684471|PMID28684471}}. The study focuses specifically on the idea that previous research has suggested that nerve - associated schwann cell precursor is a progenitor of chromaffin cells. What the findings suggested was that peripheral nerves provided migration routes for the progenitors. This is backed up by the results, a high concentration of chromaffin cells can be found being derived from the nerve, as nerve ablated mice in the experiment showed a large difference of 78% less cells compared to the control. Other than this, the study also brought to light the proliferative potential of the cells from nerves, with different other cell types being discovered as well (including cells such as parasympathetic{{#pmid:24925912|PMID24925912}} and melanocytes {{#pmid:19837037 |PMID19837037}}). The findings would provide useful information into further understanding the adrenal gland and its embryonic origins (as there is still much to learn regarding the formation of the adrenal medulla) but also pathological diseases such as neuroblastoma and pheochromatocytoma which are most common in the adrenal glandular region {{#pmid:23106811|PMID23106811}}.<br /> <br /> Link to article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6013038/<br /> <br /> ===Glossary===<br /> ----<br /> *BMP4 - Bone Morphogenic Protein 4<br /> *DOPA - Dihydroxyphenylalanine<br /> *GATA3 - Transcription factor 3 for GATA gene<br /> *GN - Ganglioneuroma<br /> *GRN - Gene Regulatory Network<br /> *HNK1 - Human Natural Killer 1<br /> *HVA - Homovanillic Acid<br /> *L-DOPA - L-3,4-dihydroxyphenylalanine<br /> *NB - Neuroblastoma<br /> *PAX - Paired Box<br /> *PCC - Pheochromocytoma<br /> *PGL - Pheochromocytoma Paraganglioma<br /> *PNMT - phenylethanolamine-N-methyltransferase <br /> *SGC - Small Granule Containing cells<br /> *SOX - Sry Box<br /> *TH - Tyrosine Hydroxylase<br /> *VMA -Vanilmandelic Acid<br /> <br /> ===Reference list===</div>

Z5091101 https://embryology.med.unsw.edu.au/embryology/index.php?title=2018_Group_Project_1&diff=358721 2018 Group Project 1 2018-10-16T11:25:42Z

<p>Z5091101: /* History */</p> <hr /> <div>=The Contribution of Neural Crest Cells to the Adrenal Medulla=<br /> ----<br /> {{2018ANAT2341ProjectHeader}}<br /> <br /> <br /> ===Introduction===<br /> <br /> ----<br /> <br /> The neural crest of an embryo migrates and differentiates to form various components of the body. This transient population of pluripotent stem-cells give rise to many complex and different structures across the adult by chemical signalling. One of these tissues is the medulla of the adrenal gland which is involved in the production of epinephrine and norepinephrine. This project will comprehensively outline the history of neural crest research, the embryonic developmental time course, tissue and organ structure, molecular mechanisms, abnormalities, animal models and current research.<br /> <br /> ===History===<br /> ----<br /> '''Describing the neural crest'''<br /> [[File:Wilhelm_His_History_Wilhelm.jpeg|left|230px|thumb|Wilhelm His]]<br /> [[File:NC Location.jpg|right|450px|thumb|The neural crest]]<br /> The "neural crest" is a structure in the embryo and is the junction between the neural and epidermal ectoderm. It is exclusive to vertebrates and forms a range of structures{{#pmid:22230617|PMID22230617}}. The neural crest contributes a large number of cells of varying structure and function that directly or indirectly contribute to the development of tissues and organs within the body {{#pmid:19179766|PMID19179766}}. In 1868, the neural crest cells were first identified in a chick embryo as a collection of cells known as "Zwischenstrang" by Professor Wilhelm His {{#pmid:22820859|PMID22820859}}. Wilhelm His was among the first to provide an explanation for the mechanics governing the developing embryo as well as the physiology and the organs that the differing germinal regions would eventually give rise to {{#pmid:19179766|PMID19179766}} This was due to his work in creating one of the first microtomes, a device that enables thin slicing of tissue. This enabled him to see embryonic tissues at greater magnifications and resolutions and gave the neural crest the name, the ganglionic crest {{#pmid:26970616|PMID26970616}}. In 1878, the term neural ridge was used to describe this collection of cells but the term neural crest was later coined by Arthur Milnes Marshall in 1879 in a paper he worked on disseminating the knowledge from his research on the development of cranial nerves in chicken embryos. {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1890s-1950s'''<br /> The neural crest is the point of origin for spinal/cranial ganglia and neurons. This theory received little criticism and was not contested much by other researchers prior to the 1890s. This is owing to the fact that the neural crest is quite closely related to the neural tube and thus this relationship makes sense. This discovery was made by His and Marshall, however, they found this out independently of one another.In the 1890s, Julia Platt, claimed that odontoblasts as well as the cartilages forming the facial and pharyngeal arch skeletons came from the ectoderm. This created much debate and was contested by many{{#pmid:22820859|PMID22820859}}. <br /> <br /> This is because this theory completely contradicted the germ-layer theory, whereby skeletal tissues originate at the mesoderm and not the ectoderm. The controversies this finding created brought about a slowing down of research, as demonstrated by a gap of almost 40 years between the theory that skeletal tissues originating from the neural crest. Today, it is known that the neural crest does indeed play a role in the development of the skeleton in vertebrates, particularly, the cranial neural crest. Although these studies were occurring, the focus was still primarily on researching pigment cells and ganglia of the spine up until the 1950s, when Sven Hörstadius' major work on the neural crest was published, titled "The Neural Crest: Its properties and derivatives in the light of experimental research". This work focused on experimental data tracing the development of the cartilaginous skeleton derived from the neural crest {{#pmid:19179766|PMID19179766}}.<br /> <br /> This period from the 1890s to the 1950s was a time of emerging research and experimentation, with various contributions of the neural crest being studied. This was done through a range of experiments involving removal of parts of the neural crest to examine the effects on development of birds and amphibians as well as transplantation of parts of neural crest to enable an understanding of patterns of cell migration {{#pmid:26970616|PMID26970616}}.<br /> <br /> '''1960s - 1970s'''<br /> In the 1960s, the migration patterns of neural crest cells were studied in avian embryos (birds). This was done through new techniques involving marking the cells with radioactive substances such as 3H-thymidine {{#pmid:26970616|PMID26970616}}. This was a shift from studying the embryos of amphibians. This was inspired by studies conducted in the 1960s on neural crest cells migrating from the brain and spinal cord, known as trunk and cranial neural crest cells {{#pmid:19179766|PMID19179766}}. The cranial neural crest eventually becomes the bones, cartilage and connective tissues forming the foundation of the face, ears and teeth. The trunk neural crest cells can either become melanocytes or can migrate into sclerotomes which are later contributors to the cartilage of the spine and the dorsal root ganglia {{#pmid:22820859|PMID22820859}}. The cells in the trunk neural crest that migrate vertically become the sympathetic ganglia, the nerves proximal to the aorta and the adrenal medulla <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. In the 1970s many detailed maps signifying the pathways of many of the neural crest cells appeared as well as an understanding that the environment in which the neural crest cells are found plays a major role in their final development as well as the occurrences of abnormalities in the fetus {{#pmid:19179766|PMID19179766}}.<br /> <br /> <br /> '''1980s - 21st century'''<br /> [[File:Regions_of_NC_Cells.jpg|left|Neural crest regions|thumb|465px]]<br /> From the 1980s-1990s, the causative agent of organ transformation from one to another (homeotic patterning), as well as the Hox genes which regulate the axis of most symmetrical animal embryos were founded and studied. The neural crest, which previously was divided into the cranial and trunk regions, was now further divided into the vagal and sacral neural crest, the cardiac neural crest and the cephalic neural crest {{#pmid:19179766|PMID19179766}}. The vagal & sacral neural crest gives rise to the parasympathetic ganglia found in the gut. Without these ganglia, peristalsis, is not possible <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. The cardiac neural crest contributes to the valves, septa and major blood vessels of the heart, as well as connective tissues and cartilage{{#pmid:19179766|PMID19179766}}. This is important for the structure of the heart as well as its overall function, enabling it to move blood around the body efficiently as well as keep pulmonary and aortic circulation separated <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> <br /> In the mid 1980s, the first studies bringing about some information on the destination of ventrally migrating neural crest cells were conducted using the antibody HNK-1, as it is known to detect antigens on neuroectodermal cells & label the migratory cells. Where previously it was thought that trunk neural crest cells migrated whilst avoiding the somites, these studies showed that the trunk neural crest cells migrated through the rostral half of each somite. How this worked was eventually understood as a result of chemotactic factors that attract and repel the cells to follow this migration {{#pmid:26970616|PMID26970616}}.<br /> <br /> <br /> Today, knowledge of the neural crest cells, their migration patterns, modes of differentiation, derivatives and apoptosis (cell death) are being studied extensively. This is being done on a comparative basis between different organisms, to add further evidence for evolution {{#pmid:19179766|PMID19179766}}. The neural crest is definitely forging a "crest" between the fields of developmental and evolutionary biology, as it is a structure '''shared exclusively by all vertebrates'''. Invertebrates do not derive their specialised cells from the neural crest as they do not have one, rather, they derive these from the endomesoderm {{#pmid:22230617|PMID22230617}}.<br /> <br /> <br /> '''Future directions'''<br /> <br /> Since its discovery by His, the neural crest field has made great progress, from studies performed on the structure, to analysis of the molecules and whether certain aspects of the neural crest are specific to a single species of organism, or to all vertebrates collectively. Future work on the cranial neural crest needs to be done as well as identifying and categorising the networks responsible for the proliferation and death of cells, as well as how the cells move and migrate, as well as the gene regulatory networks (GRNs) that regulate the synthesis of proteins {{#pmid:22230617|PMID22230617}}.<br /> . Advances in technology will undeniably lead us to more answers on the subject and studies that include imaging, mathematical and molecular modelling will greatly enhance our growing understanding of how neural crest cells move {{#pmid:26970616|PMID26970616}}.<br /> <br /> ===Developmental time course===<br /> ---- <br /> <br /> [[File:Adrenal_Medulla_Developmental_Timeline.jpg|right|thumb|500px]]<br /> <br /> The adrenal gland has two distinct sections, the cortex and the medulla, both with different embryonic origins. The cortex accounts for 90% of the adrenal glands and arises from intermediate mesoderm. The medulla only accounts for 10% of the adult adrenal glands, however it has neural crest embryonic origin. The medulla consists of chromaffinoblast cells which are migrant neuroblast cells from the neural crest, therefore the adrenal medulla is a component of the sympathetic nervous system.{{#pmid:21175739|PMID21175739}} Neural crest cells replicate in week 7 and begin to differentiate in week 8, the cells then migrate to the developing adrenal gland in week 9 of development.{{#pmid:25255746|PMID25255746}}{{#pmid:18279781|PMID18279781}} The neural crest cells infiltrate the cortex and the chromaffin cells are scattered islands in the cortex.{{#pmid:23354096|PMID23354096}} Throughout development the cells will become more compact in the centre of the gland, during this period of development the adrenal gland is growing rapidly. The gland is abnormally large until the second trimester and the medulla is much thicker prenatally.{{#pmid:18279781|PMID18279781}}{{#pmid:21175739|PMID21175739}}<br /> <br /> <br /> ===Embryonic origins===<br /> ----<br /> [[File:Trunk_NCC_migration.jpg|left|450px|thumb|Trunk NCC migration]]<br /> The adrenal gland is made up of the adrenal cortex and adrenal medulla, which both have different embryonic origins. The adrenal medulla arises from the neural crest tissue, found near the level of the coeliac plexus & sympathetic ganglion at somites 18-24 {{#pmid:16124976|PMID16124976}}. Specifically, this neural crest tissue comes from the trunk neural crest cells (see above figure to determine the approximate location in an embryo) <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> The trunk neural crest coordinates the development of the endocrine system, secretory cells, the peripheral nervous system and, to some degree, skeletal development, as well as innervation of the intestine {{#pmid: 28287247|PMID 28287247}}. The trunk neural cells arise caudally, undergo an epithelial to mesenchymal transition and follow three migratory pathways {{#pmid:20399766|PMID20399766}}.<br /> [[File:Differentiation_of_NCC.jpg|left|580px|thumb|Differentiation of chromaffin cells]]<br /> - A dorsolateral pathway (between ectoderm and somites), these become melanocytes, travel up to the point of the dermis and become a major part of the hair follicles and skin <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> - A ventrolateral pathway (through the somites)<br /> - A ventromedial pathway (between neural tube and posterior schlerotome){{#pmid:20399766|PMID20399766}}.<br /> <br /> Migration of neural crest cells from the sympathetic ganglion is what leads to the development of the adrenal medulla. In week 8 of development, immature cells called neuroblasts migrate through to the inner portion of the medulla, where they become the adrenal medulla {{#pmid:19683477|PMID19683477}}. Chromaffin cells are neuroendocrine cells and are found in the sympathetic ganglia and make up the majority of the adrenal medulla{{#pmid:19683477|PMID19683477}}. They synthesise and release a range of hormones in the body and arise from the temporary neural crest. The term chromaffin was inspired by the staining capacity of these cells when they came into contact with chrome salts. They make, store, export and use catecholamines, responsible for making noradrenaline and originate at the caudal region of somites 18-24 of the neural crest, also known as the adrenomedullary region {{#pmid:19683477|PMID19683477}}.<br /> <br /> For cells to leave the neural crest and begin their migration, certain conditions need to be met, that is, the cells need to be loosely connected, their tight junctions becoming relaxed, initiated by "Slug protein" and a loss of N-Cadherin which also leads to the loosening of these junctions. The surrounding matrix as well as chemotactic and stem cell factors of the neural tube are then what dictates how the neural crest cells move, some proteins stopping their migration to that area and others encouraging the movement <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. After splitting apart, the first neural crest cells move ventrally and pass into the spaces between the somites and then, through the anterior portions of each segment until they arrive at the para-aortic sites, where they become the cells of the sympathetic ganglia and the adrenal medulla {{#pmid:19683477|PMID19683477}}. BMP-4 (bone morphogenetic protein 4) then acts on these neural crest cells, preventing them from becoming cells that have a neural function and causing them to become chromaffin cells at the adrenal medulla. Glucocorticoids then play a role in maintenance of chromaffin cells in postnatal life, this was only found recently, as previously it was thought that glucocorticoids were responsible entirely for the differentiation of neural crest cells into chromaffin, or adrenomedullary cells {{#pmid:23220335|PMID23220335}}.<br /> <br /> ===Anatomy and Functions===<br /> <br /> ----<br /> <br /> ====Anatomy and Histology====<br /> <br /> The adrenal medulla makes up the inner section of the adrenal glands, and is surrounded by the cortex, and a connective tissue capsule. It lies in the centre of the gland and it rarely measures no more than 2mm in thickness {{#pmid:21107679|PMID21107679}}. The cells of the adrenal medulla are derived from the neural crest as opposed to the mesodermal origins of the cortex. The adrenal medulla contains secretory cells called chromaffin cells due to the agents they produce when oxidised, such as chromate {{#pmid:11215683|PMID11215683}}. These cells secrete epinephrine, norepinephrine, chromogranin and neuropeptides in response to various substances such as acetylcholine <ref name="PMID11215683"/>. [[File:ADRENAL MEDULLA .jpg|600px|thumb|right|Adrenal Medulla Histology]]<br /> <br /> There are many types of highly differentiated cells in the adult adrenal medulla: <br /> - Epinephrine cells (90% of all chromaffin cells) {{#pmid:24715564|PMID24715564}}<br /> - Norepinephrine cells (10% of all chromaffin cells) <ref name="PMID24715564"/><br /> - Small granule-containing cells (SGCs) <ref name="PMID11215683"/><br /> <br /> These cells also synthesise, store and secrete catecholamines through controlled and regulated pathways <ref name="PMID24715564"/>, such as various peptides like substance P and neurotensin.These cells have unique neuroendocrine characteristics as a result of their neural-crest origin. They receive preganglionic innervation by thoracic splanchnic nerves, and could almost be considered a specialised sympathetic ganglion. With postganglgionic bodies, cells of the medulla are densely clustered around their vasculature for the secretion of hormones into the bloodstream to moderate the concentration of epinephrine and norepinephrine. The adrenal medulla also contains presynaptic sympathetic ganglion cells <ref name="PMID11215683"/>. The small granule-containing cells are usually found in clusters whereas, the ganglion cells are found either individually or in clusters, usually dispersed among the chromaffin cells or among the nerve fibres {{#pmid:18021328|PMID18021328}}. During embryonic development (around weeks 9-12), in contrast to the developing adrenal cortex, the medulla does not show evidence of an organised structure other than a small cluster of cells scattered throughout its cortex {{#pmid:30247985|PMID30247985}}. <br /> <br /> <br /> <br /> ====Related Anatomy====<br /> <br /> The tissue and organ structure of the adrenal medulla should be understood with regard to its specialised function within the sympathetic nervous system. <br /> <br /> The medullary region of the adrenal glands is tasked with the endocrine secretions of adrenaline and nor-adrenaline in response to environmental stressors that are signalled for by the sympathetic nervous system. That is, the secretion of fight-or-flight response hormones in order to restrict vasculature to the trunk and increase vascular activity in the peripheral musculature.<br /> <br /> The adrenal glands are supplied by several branches of the great vessels in the abdominal cavity. The secreted catecholamines in the medulla are directly able to pass to the blood stream this way.<br /> <br /> These adrenal glands and their contents are retroperitoneal in the adult and varied in shape, with the left often being semilunar and right being pyramidal. Nervous supply of the adrenal glands is achieved by contributions from the splanchnic nerves of the celiac plexus. {{#pmid:11215683|PMID11215683}} <br /> <br /> [[File:Dd.jpg|400px|thumb|right|Adult Adrenal Glands in situ]] <br /> ----<br /> ====Role of the Adrenal Medulla====<br /> <br /> Understanding the biochemistry of catecholamines is necessary to see how the adrenal medulla is designed in the stages of embryology and how it is suited for life in the neonate and adult. <br /> <br /> The epinephrine and norepinephrine in the neonate and adult work by primarily changing the osmoregulatory state of vasculature in organs. With the exclusion of their neuromodulatory and neurotransmitter functions, epinephrine and norepinephrine are mainly tasked with the control of sympathetic and parasympathetic supplies. <br /> <br /> Norepinephrine is a constrictor of peripheral vasculature by antagonising the action of surface receptors expressed on the endothelium of blood vessels, specifically Alpha-1 and Alpha-2 receptors, such that vascular resistance increases. <br /> <br /> Epinephrine is both a vasoconstrictor and vasodilator, depending on what receptors it attaches to. As a non-selective adrenergic agonist, it acts on Alpha-1, Alpha-2, Beta-1, Beta-2 and Beta-3 receptors that are found throughout the body's tissues, yielding many different physiological responses. {{#pmid:19396395|PMID19396395}}<br /> <br /> '''Adult Function'''<br /> <br /> While the adrenal cortex releases glucocorticoids in response to long term stress, the adrenal medulla releases its hormones in response to short-term, acute stress. The adrenal medulla contains the neuroendocrine chromaffin cells which are responsible for secreting adrenaline and noradrenaline. The function of these hormones is primarily to maintain the body’s homeostasis, especially of the internal organs, and to properly activate the autonomic stress response, more commonly known as the ‘fight or flight’ response {{#pmid:30237243|PMID30237243}}. Thus the function of the medulla includes signalling the liver and skeletal muscles to convert glycogen into glucose for increased energy. This results in increased blood glucose levels. These hormones also increase the heart rate, pulse and blood pressure in preparation for the fight or flight response. In addition to this, these hormones dilate the lung airways and prompt vasodilation to further increase oxygenation of important organs such as the lung, brain and heart. Vasoconstriction of blood vessels is also prompted to other less essential organs such as the bladder and the digestive system.<br /> <br /> Other effects also include pupil dilation, dry mouth and a loss in peripheral vision <ref name="PMID18021328"/>. Paramount to the correct response of chromaffin cells is the synaptic connection of the preganglionic cells which originate from the central nervous system and project axons into the adrenal medulla. While this is a very important relationship, the mechanisms of this remains unknown <ref name="PMID30237243"/>. In addition to the release of catecholamines, cells in the medulla also release peptides through the process of exocytosis from chromaffin granules, to help regulate blood pressure and regulation throughout the body. These peptides also regulate the release of adrenaline and noradrenaline, blood vessel contraction and the immune response <ref name="PMID18021328"/>. <br /> <br /> '''Embryonic function'''<br /> <br /> The current knowledge about the development of the adrenal gland is limited, with nearly all models being from animals, and very limited functional data available from human fetal adrenals <ref name="PMID30247985"/>. Thus for these reasons, there is scarce information available on the embryonic adrenal medullary functions. Nevertheless, there is accumulating evidence that the catecholamines in the fetal adrenal medulla plays an important role in the time of delivery by controlling thermogenesis and heart regulation {{#pmid:6998630|PMID6998630}}. <br /> <br /> The hormones released by the medulla during birth also play a key role for the newborn’s adaptation to extrauterine life. Despite the immaturity of the adrenal medulla at birth, it is known that respiratory, metabolic and cardiovascular changes during delivery are dependent on the adrenomedullary hormones {{#pmid:3280659|PMID3280659}}. Experimental data from human and animal fetal research shows that the fetal sympathoadrenal system, consisting of the adrenal medulla, sympathetic neurons and chromaffin tissue work together to maintain fetal homeostasis {{#pmid:6346884|PMID6346884}}. The adrenal medulla thus appears to provide vital physiological functions for fetal and neonatal survival, especially during birth. <br /> <br /> <br /> ----<br /> <br /> ===Molecular mechanisms/factors/genes===<br /> ----<br /> <br /> ====Genes and Transcription Factors Involved with the Adrenal Medulla's Development====<br /> <br /> The 'story' of the Adrenal Medulla's neural crest tissue begins at the process of neurulation, the formation of the neural tube from the folding neural plate, which is comprised of developing ectoderm which is opposite to the primitive streak. It is here that several key chemical players are at work. The classic interpretation of Sonic Hedgehog (Shh) and Wnt signalling pathways as the only mediators here, has been shown to be incorrect. Research has uncovered other signallers such as: <br /> <br /> *Bone-Morphogenic-Protein-4 (BMP4) for the regional expression of nervous system distinctions in the growing neural plate. This maintains two important embryonic trancription factors known as Paired-Box (PAX) Genes 3 and 7 which can allow for expression of neural crest markers HNK-1, SRY-Box (SOX) 8, 9 and 10 as the neural tube closes and the neural crest delaminates from the folding. {{#pmid:16688176|PMID16688176}} <br /> <br /> *Slug via Wnt signalling, this allows for the loosening of gap junctions in the extracellular matrix surrounding the newly-formed neural tube and trunk of the embryo. This extracellular matrix has chemo-attractant molecules<br /> <br /> [[File:Catecholamine_Synthesis.jpg|400px|thumb|right|Biochemical Cascade of Catecholamine Synthesis]]<br /> <br /> The importance of Somitogenesis and Neural Crest come to a head when neural crest cells must migrate anteriorly past somites 18 to 24 <br /> <br /> Members of the SOX gene family have multiple key contributors to Neural Crest in the Adrenal Medulla.<br /> <br /> <br /> Mouse models have demonstrated that SOX-10 knock-outs (mice whose DNA has been engineered to not express SOX-10) do not have an adrenal medulla. There has also been suggestion that SOX-8,9 and 10 are all strongly related to the migratory patterning of neural crest cells to the developing adrenal glands. {{#pmid:18272785|PMID18272785}}<br /> <br /> The TH gene (for Tyrosine Hydroxylase) encodes the aforementioned enzyme in the adrenal medulla and central nervous system. Tyrosine Hydroxylase is crucial in biochemical pathways and cascades for the synthesis of catecholamines and other CNS neurotransmitters. The conversion from L-Tyrosine to L-DOPA is dependent upon the catalytic action of Tyrosine Hydroxylase. From there, L-DOPA can make Dopamine and eventually Epinephrine and Norepinephrine as well. {{#pmid:19396395|PMID19396395}}<br /> <br /> ===Abnormalities/abnormal development===<br /> ----<br /> <br /> Abnormalities of the Adrenal Medulla are much less common than its mesoderm-derived shell of the Adrenal Gland. Three of the most notorious abnormalities of the Adrenal Medulla include:<br /> <br /> * Pheochromocytomas<br /> * Ganglioneuromas<br /> * Neuroblastomas<br /> <br /> <br /> Pheochromocytomas (PCCs) are variable neoplasias of the adrenal medulla's chromaffin cells. There are many classifications of PCCs, with autosomal-dominant germ-line mutations and heredities being one of the main causes. Familial pheochromocytoma-paraganglioma (PGL) syndromes exist, with PGL1 having mutations of the SDHD gene, PGL3 being mutated of the SDHC gene and PGL4 having mutation of the SDHB gene. These phenotypically present as extra-adrenal chromaffin bodies, malformation of the adrenal glands themselves, absence of chromaffin bodies and fluctuations in circulating catecholamines. {{#pmid:18021328|PMID18021328}}<br /> <br /> Ganglioneuromas (GNs) are classically-benign growths that are very rare and arise from neural crest tissue. They are not circumscribed to the adrenal medulla, but also are found in the sympathetic chain and trunk ganglia. As a result of their scarcity, not much is known about them other than a few aberrant genes and generic clinical presentations. ERBB3, the receptor tyrosine kinas is understood to be important in the development of GNs, as well as an extremely high prevalence of up-regulated GATA3. A key thing to note is also the '''lack''' of N-MYC expression in GNs, which is quite prominent in neuroblastomas and other neoplasias. {{#pmid:29085827|PMID29085827}} {{#pmid:23715162|PMID23715162}} <br /> <br /> Neuroblastomas (NBs) are a more aggressive form of cancer, derived from neuroblasts - the precursor cells to neurons. A rather common pediatric cancer, they are often in children who are in risk factor groups such as those with aforementioned familial cancer syndromes, neurofibromatosis-1. These tumours often present with extremely variable catecholamine concentrations, which has implications for blood pressure, heart contractility and much more. Urinary excretion of norepinephrine, homovanillic acid (HVA) and vanilmandelic acid (VMA) can be used to help diagnose a suspected lesion of the adrenal gland, as these chemicals are associated with altered chemical cascades that are suspicious of neuroblastic change. {{#pmid:16372223|PMID16372223}}<br /> <br /> <br /> Apart from these abnormalities, there are other pathologies that may be connected to the adrenal medulla. One such example is a pathology of the Organ of Zuckerkandl. Also known as the para-aortic body, the Organ of Zuckerkandl is a primarily-gestational organ comprised of chromaffin cells and serves a similar purpose to the adrenal medulla in neonatal life.<br /> <br /> ===Animal models===<br /> ----<br /> Animal models are an integral part of research in embryology. In particular due to the moral concerns regarding the use of humans in scientific research. As a result different animals are used as substitutes to simulate the same environments and hope to achieve results that would also be able to represent humans as well. Prenatal adrenal gland development has been described in a number of scientific reports dating from the 1900s to studies in more recent years. These involved a variety of animal models such as ox, sheep, swine and most commonly mice. <br /> <br /> ====Chromaffin cells====<br /> There has been extensive research conducted into the adrenal chromaffin cells and their embryological developments. As explained above nueral crest cells are pluripotent meaning they are able to differentiate into multiple different cells{{#pmid:19377845|PMID19377845}}. The neural crest cells give rise to chromaffin cells of the adrenal medulla.<br /> <br /> =====Rat Models=====<br /> [[File:Adrenal gland.png|300px|thumb|right|3D images showing TH - positive cells accumulating at the cranial and Caudal ends of the adrenal gland.]]<br /> Previous research has reported that nueral crest cells differentiate into chromaffin cells around 19 days of gestation before forming the adrenal medulla{{#pmid:28684471|PMID2868441}}. Past research had also suggested that neural crest derived adrenal gland cells migrate using the sympathetic ganglia to the adrenal gland or preaortic ganglion, following different pathways, to reach their specific destination. However the results have shown that the pathways used to reach its destinations overlapped. This would suggest that there is a possibility of the cells using the same pathway to move from the beginning production to the destination that is the adrenal medulla (for chromaffin cells) and the preaortic ganglion (other cells involved in the sympathetic system). <br /> <br /> One particular study done by M.Yamato in 2004, along with his fellow scientists attempted to study the migration of neural crest cells in Wistar rats. In order to observe the formation adrenal medulla from the neural crest cells during the embryonic period, Yamato used anti - tyrosine hydroxylase (TH) antiserum injected into the rat embryos between 13-17 days of gestation. The anti - TH antiserum stain allows the scientists to visualize the neural crest cells under a light microscope. Later three dimensional images were created. From the images observed between 13 to 15 days of gestation, the TH - positive cells can be seen to move from the dorsal to the adrenal primordium{{#pmid:15240937|PMID15240937}}. After 16 days it was observed that a capsule had formed in some parts and TH - positive cells had penetrated the adrenal gland{{#pmid:15240937|PMID15240937}}. At seventeen days, TH - positive cells can be seen collecting at the medial part of the adrenal gland. The reconstructed images also shows that at the later stages during the 16-17 days of gestation, the accumulation of TH - positive cells grow and in combination with cell division leads to the formation of the adrenal medulla.<br /> <br /> =====Chicken models=====<br /> Chicken and rat models are often the most commonly used models when dealing with neural crest cells. A particle review article, collates multiple researchers results and presents evidence to discuss previous information suggesting that sympathetic neurons and chromaffin cells do not share a common progenitor{{#pmid:3693940|PMID3693940}}. The relevant study involved the use of cell cultures, Sympathoadrneal (SA) progenitor cells from embryonic(from chick embryos) and eary developmental stages were able to be procured. From these cultures it was easy to identify that glucocorticoids were crucial in the differentiation of SA cells into their derivatives, sympathetic neurons and chromaffin cells.<br /> <br /> [[File:Expression of BMP protein 4 .jpg|300px|thumb|right|Shows the movement of the chromaffin progenitors moving from each stage of development. sg: sympathetic ganglia ac:adrenal cortical region ag: adrenal gland da: dorsal aortic region]]<br /> <br /> Another study conducted deals with the role of the bone morphogenetic protein(BMP-4) and its importance in the development of the adrenal medullary cells, chromaffin cells{{#pmid:18945349|PMID18945349}}. Previous research had shown that BMP - 4 a growth factor is plays an important role in the regulation of chromaffin cell production{{#pmid:10679774|PMID10679774}}. The researchers incubated chick embryos for 3 - 9 embryonic days and dissected them to be used for tissue cultures. Embryonic day 8 chick embryos had BMP - 4 overexpressing cells implanted in the sympathetic ganglia area, as well as other neurons which contained chromaffin like cells. What was observed was an increase in size and numbers of 'chromaffin' granules{{#pmid:18945349|PMID18945349}}. As a result it was concluded that although BMP - 4 promotes certain chromaffin traits, it does not have the capability to convert sympathetic neurons into a chromaffin type cell.<br /> <br /> ===Current research (labs)===<br /> ----<br /> <br /> ==== Generation of Adrenal Chromaffin-like Cells from Human Pluripotent Stem Cells====<br /> <br /> As explained above the adrenal medulla plays an important part in the autonomic system of an adult human. The chromaffin cells, in particular, are important neural crest derived cell that is closely related to the adrenal medulla. Previous findings have focused specifically on the mechanisms controlling the neural crest cell migration and how these cells go on to form the different derivatives in their particular destinations in the embryo. For example, as previously explained studies have shown that chromaffin cells have been observed to move to the adrenal gland to form the medulla of the adrenal gland. This report goes through a recent study that involves the adrenal medullary cells, in particular chromaffin cells, and their potential to be used to model certain pathological diseases related to these cells. This is part of a study that also involves neural crest cells and their ability to differentiate into multiple different types of cells<ref>Lumb, R., & Schwarz, Q. (2015). Sympathoadrenal neural crest cells: The known, unknown and forgotten?. Development, Growth & Differentiation, 57(2), 146-157. doi: 10.1111/dgd.12189</ref>. Neural crest cells and SAPs from human embryonic cells and induced pluripotent stem cells were generated to be used in the experiment. By exposing the pluripotent stem cells to BMP4 in vitro, results showed that these cells would 'upregulate' the chromaffin cell - specific marker PMNT (an enzyme that synthesizes adrenaline). Furthermore when the cells from human embryos were implanted into avian embryos, there was a visible potential for the human cells to differentiate into cells that expressed the chromaffin cell markers{{#pmid:5768882|PMID5768882}}.<br /> <br /> Link to article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768882/<br /> <br /> ====Multipotent Peripheral Glial Cells Generate Neuroendocrine Cells of the Adrenal Medulla====<br /> <br /> Similar to the first study, this one also focuses on the chromaffin cells and their relationship to the adrenal medulla. Chromaffin cells often represent the main endocrine component that is believed to differentiate from neural crest cells{{#pmid:28684471|PMID28684471}}. The study focuses specifically on the idea that previous research has suggested that nerve - associated schwann cell precursor is a progenitor of chromaffin cells. What the findings suggested was that peripheral nerves provided migration routes for the progenitors. This is backed up by the results, a high concentration of chromaffin cells can be found being derived from the nerve, as nerve ablated mice in the experiment showed a large difference of 78% less cells compared to the control. Other than this, the study also brought to light the proliferative potential of the cells from nerves, with different other cell types being discovered as well (including cells such as parasympathetic{{#pmid:24925912|PMID24925912}} and melanocytes {{#pmid:19837037 |PMID19837037}}). The findings would provide useful information into further understanding the adrenal gland and its embryonic origins (as there is still much to learn regarding the formation of the adrenal medulla) but also pathological diseases such as neuroblastoma and pheochromatocytoma which are most common in the adrenal glandular region {{#pmid:23106811|PMID23106811}}.<br /> <br /> Link to article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6013038/<br /> <br /> ===Glossary===<br /> ----<br /> *BMP4 - Bone Morphogenic Protein 4<br /> *DOPA - Dihydroxyphenylalanine<br /> *GATA3 - Transcription factor 3 for GATA gene<br /> *GN - Ganglioneuroma<br /> *GRN - Gene Regulatory Network<br /> *HNK1 - Human Natural Killer 1<br /> *HVA - Homovanillic Acid<br /> *L-DOPA - L-3,4-dihydroxyphenylalanine<br /> *NB - Neuroblastoma<br /> *PAX - Paired Box<br /> *PCC - Pheochromocytoma<br /> *PGL - Pheochromocytoma Paraganglioma<br /> *PNMT - phenylethanolamine-N-methyltransferase <br /> *SGC - Small Granule Containing cells<br /> *SOX - Sry Box<br /> *TH - Tyrosine Hydroxylase<br /> *VMA -Vanilmandelic Acid<br /> <br /> ===Reference list===</div>

Z5091101 https://embryology.med.unsw.edu.au/embryology/index.php?title=2018_Group_Project_1&diff=358521 2018 Group Project 1 2018-10-16T07:34:54Z

<p>Z5091101: /* History */</p> <hr /> <div>=The Contribution of Neural Crest Cells to the Adrenal Medulla=<br /> ----<br /> {{2018ANAT2341ProjectHeader}}<br /> <br /> <br /> ===Introduction===<br /> <br /> ----<br /> <br /> The neural crest of an embryo migrates and differentiates to form various components of the body. This transient population of pluripotent stem-cells give rise to many complex and different structures across the adult by chemical signalling. One of these tissues is the medulla of the adrenal gland which is involved in the production of epinephrine and norepinephrine. This project will comprehensively outline the history of neural crest research, the embryonic developmental time course, tissue and organ structure, molecular mechanisms, abnormalities, animal models and current research.<br /> <br /> ===History===<br /> ----<br /> '''Describing the neural crest'''<br /> [[File:Wilhelm_His_History_Wilhelm.jpeg|left|230px|thumb|Wilhelm His]]<br /> [[File:NC Location.jpg|right|450px|thumb|The neural crest]]<br /> The "neural crest" is a structure in the embryo and is the junction between the neural and epidermal ectoderm. It is exclusive to vertebrates and forms a range of structures{{#pmid:22230617|PMID22230617}}. The neural crest contributes a large number of cells of varying structure and function that directly or indirectly contribute to the development of tissues and organs within the body {{#pmid:19179766|PMID19179766}}. In 1868, the neural crest cells were first identified in a chick embryo as a collection of cells known as "Zwischenstrang" by Professor Wilhelm His {{#pmid:22820859|PMID22820859}}. Wilhelm His was among the first to provide an explanation for the mechanics governing the developing embryo as well as the physiology and the organs that the differing germinal regions would eventually give rise to {{#pmid:19179766|PMID19179766}} This was due to his work in creating one of the first microtomes, a device that enables thin slicing of tissue. This enabled him to see embryonic tissues at greater magnifications and resolutions and gave the neural crest the name, the ganglionic crest {{#pmid:26970616|PMID26970616}}. In 1878, the term neural ridge was used to describe this collection of cells but the term neural crest was later coined by Arthur Milnes Marshall in 1879 in a paper he worked on disseminating the knowledge from his research on the development of cranial nerves in chicken embryos. {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1890s-1950s'''<br /> The neural crest is the point of origin for spinal/cranial ganglia and neurons. This theory received little criticism and was not contested much by other researchers prior to the 1890s. This is owing to the fact that the neural crest is quite closely related to the neural tube and thus this relationship makes sense. This discovery was made by His and Marshall, however, they found this out independently of one another.In the 1890s, Julia Platt, claimed that odontoblasts as well as the cartilages forming the facial and pharyngeal arch skeletons came from the ectoderm. This created much debate and was contested by many{{#pmid:22820859|PMID22820859}}. <br /> <br /> This is because this theory completely contradicted the germ-layer theory, whereby skeletal tissues originate at the mesoderm and not the ectoderm. The controversies this finding created brought about a slowing down of research, as demonstrated by a gap of almost 40 years between the theory that skeletal tissues originating from the neural crest. Today, it is known that the neural crest does indeed play a role in the development of the skeleton in vertebrates, particularly, the cranial neural crest. Although these studies were occurring, the focus was still primarily on researching pigment cells and ganglia of the spine up until the 1950s, when Sven Hörstadius' major work on the neural crest was published, titled "The Neural Crest: Its properties and derivatives in the light of experimental research". This work focused on experimental data tracing the development of the cartilaginous skeleton derived from the neural crest {{#pmid:19179766|PMID19179766}}.<br /> <br /> This period from the 1890s to the 1950s was a time of emerging research and experimentation, with various contributions of the neural crest being studied. This was done through a range of experiments involving removal of parts of the neural crest to examine the effects on development of birds and amphibians as well as transplantation of parts of neural crest to enable an understanding of patterns of cell migration {{#pmid:26970616|PMID26970616}}.<br /> <br /> '''1960s - 1970s'''<br /> In the 1960s, the migration patterns of neural crest cells were studied in avian embryos (birds). This was done through new techniques involving marking the cells with radioactive substances such as 3H-thymidine {{#pmid:26970616|PMID26970616}}. This was a shift from studying the embryos of amphibians. This was inspired by studies conducted in the 1960s on neural crest cells migrating from the brain and spinal cord, known as trunk and cranial neural crest cells {{#pmid:19179766|PMID19179766}}. The cranial neural crest eventually becomes the bones, cartilage and connective tissues forming the foundation of the face, ears and teeth. The trunk neural crest cells can either become melanocytes or can migrate into sclerotomes which are later contributors to the cartilage of the spine and the dorsal root ganglia {{#pmid:22820859|PMID22820859}}. The cells in the trunk neural crest that migrate vertically become the sympathetic ganglia, the nerves proximal to the aorta and the adrenal medulla <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. In the 1970s many detailed maps signifying the pathways of many of the neural crest cells appeared as well as an understanding that the environment in which the neural crest cells are found plays a major role in their final development as well as the occurrences of abnormalities in the fetus {{#pmid:19179766|PMID19179766}}.<br /> <br /> <br /> '''1980s - 21st century'''<br /> [[File:Regions_of_NC_Cells.jpg|left|Neural crest regions|thumb|465px]]<br /> From the 1980s-1990s, the causative agent of organ transformation from one to another (homeotic patterning), as well as the Hox genes which regulate the axis of most symmetrical animal embryos were founded and studied. The neural crest, which previously was divided into the cranial and trunk regions, was now further divided into the vagal and sacral neural crest, the cardiac neural crest and the cephalic neural crest {{#pmid:19179766|PMID19179766}}. The vagal & sacral neural crest gives rise to the parasympathetic ganglia found in the gut. Without these ganglia, peristalsis, is not possible <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. The cardiac neural crest contributes to the valves, septa and major blood vessels of the heart, as well as connective tissues and cartilage{{#pmid:19179766|PMID19179766}}. This is important for the structure of the heart as well as its overall function, enabling it to move blood around the body efficiently as well as keep pulmonary and aortic circulation separated <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> <br /> <br /> Today, knowledge of the neural crest cells, their migration patterns, modes of differentiation, derivatives and apoptosis (cell death) are being studied extensively. This is being done on a comparative basis between different organisms, to add further evidence for evolution {{#pmid:19179766|PMID19179766}}. The neural crest is definitely forging a "crest" between the fields of developmental and evolutionary biology, as it is a structure '''shared exclusively by all vertebrates'''. Invertebrates do not derive their specialised cells from the neural crest as they do not have one, rather, they derive these from the endomesoderm {{#pmid:22230617|PMID22230617}}.<br /> <br /> '''Future directions'''<br /> <br /> Since its discovery by His, the neural crest field has made great progress, from studies performed on the structure, to analysis of the molecules and whether certain aspects of the neural crest are specific to a single species of organism, or to all vertebrates collectively. Future work on the cranial neural crest needs to be done as well as identifying and categorising the networks responsible for the proliferation and death of cells, as well as how the cells move and migrate, as well as the gene regulatory networks (GRNs) that regulate the synthesis of proteins. Advances in technology will undeniably lead us to more answers on the subject {{#pmid:22230617|PMID22230617}}.<br /> <br /> ===Developmental time course===<br /> ---- <br /> <br /> [[File:Adrenal_Medulla_Developmental_Timeline.jpg|right|thumb|500px]]<br /> <br /> The adrenal gland has two distinct sections, the cortex and the medulla, both with different embryonic origins. The cortex accounts for 90% of the adrenal glands and arises from intermediate mesoderm. The medulla only accounts for 10% of the adult adrenal glands, however it has neural crest embryonic origin. The medulla consists of chromaffinoblast cells which are migrant neuroblast cells from the neural crest, therefore the adrenal medulla is a component of the sympathetic nervous system.{{#pmid:21175739|PMID21175739}} Neural crest cells replicate in week 7 and begin to differentiate in week 8, the cells then migrate to the developing adrenal gland in week 9 of development.{{#pmid:25255746|PMID25255746}}{{#pmid:18279781|PMID18279781}} The neural crest cells infiltrate the cortex and the chromaffin cells are scattered islands in the cortex.{{#pmid:23354096|PMID23354096}} Throughout development the cells will become more compact in the centre of the gland, during this period of development the adrenal gland is growing rapidly. The gland is abnormally large until the second trimester and the medulla is much thicker prenatally.{{#pmid:18279781|PMID18279781}}{{#pmid:21175739|PMID21175739}}<br /> <br /> <br /> ===Embryonic origins===<br /> ----<br /> [[File:Trunk_NCC_migration.jpg|left|450px|thumb|Trunk NCC migration]]<br /> The adrenal gland is made up of the adrenal cortex and adrenal medulla, which both have different embryonic origins. The adrenal medulla arises from the neural crest tissue, found near the level of the coeliac plexus & sympathetic ganglion at somites 18-24 {{#pmid:16124976|PMID16124976}}. Specifically, this neural crest tissue comes from the trunk neural crest cells (see above figure to determine the approximate location in an embryo) <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> The trunk neural crest coordinates the development of the endocrine system, secretory cells, the peripheral nervous system and, to some degree, skeletal development, as well as innervation of the intestine {{#pmid: 28287247|PMID 28287247}}. The trunk neural cells arise caudally, undergo an epithelial to mesenchymal transition and follow three migratory pathways {{#pmid:20399766|PMID20399766}}.<br /> [[File:Differentiation_of_NCC.jpg|left|580px|thumb|Differentiation of chromaffin cells]]<br /> - A dorsolateral pathway (between ectoderm and somites), these become melanocytes, travel up to the point of the dermis and become a major part of the hair follicles and skin <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> - A ventrolateral pathway (through the somites)<br /> - A ventromedial pathway (between neural tube and posterior schlerotome){{#pmid:20399766|PMID20399766}}.<br /> <br /> Migration of neural crest cells from the sympathetic ganglion is what leads to the development of the adrenal medulla. In week 8 of development, immature cells called neuroblasts migrate through to the inner portion of the medulla, where they become the adrenal medulla {{#pmid:19683477|PMID19683477}}. Chromaffin cells are neuroendocrine cells and are found in the sympathetic ganglia and make up the majority of the adrenal medulla{{#pmid:19683477|PMID19683477}}. They synthesise and release a range of hormones in the body and arise from the temporary neural crest. The term chromaffin was inspired by the staining capacity of these cells when they came into contact with chrome salts. They make, store, export and use catecholamines, responsible for making noradrenaline and originate at the caudal region of somites 18-24 of the neural crest, also known as the adrenomedullary region {{#pmid:19683477|PMID19683477}}.<br /> <br /> For cells to leave the neural crest and begin their migration, certain conditions need to be met, that is, the cells need to be loosely connected, their tight junctions becoming relaxed, initiated by "Slug protein" and a loss of N-Cadherin which also leads to the loosening of these junctions. The surrounding matrix as well as chemotactic and stem cell factors of the neural tube are then what dictates how the neural crest cells move, some proteins stopping their migration to that area and others encouraging the movement <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. After splitting apart, the first neural crest cells move ventrally and pass into the spaces between the somites and then, through the anterior portions of each segment until they arrive at the para-aortic sites, where they become the cells of the sympathetic ganglia and the adrenal medulla {{#pmid:19683477|PMID19683477}}. BMP-4 (bone morphogenetic protein 4) then acts on these neural crest cells, preventing them from becoming cells that have a neural function and causing them to become chromaffin cells at the adrenal medulla. Glucocorticoids then play a role in maintenance of chromaffin cells in postnatal life, this was only found recently, as previously it was thought that glucocorticoids were responsible entirely for the differentiation of neural crest cells into chromaffin, or adrenomedullary cells {{#pmid:23220335|PMID23220335}}.<br /> <br /> ===Anatomy and Functions===<br /> <br /> ----<br /> <br /> ====Anatomy and Histology====<br /> <br /> The adrenal medulla makes up the inner section of the adrenal glands, and is surrounded by the cortex, and a connective tissue capsule. It lies in the centre of the gland and it rarely measures no more than 2mm in thickness {{#pmid:21107679|PMID21107679}}. The cells of the adrenal medulla are derived from the neural crest as opposed to the mesodermal origins of the cortex. The adrenal medulla contains secretory cells called chromaffin cells due to the agents they produce when oxidised, such as chromate {{#pmid:11215683|PMID11215683}}. These cells secrete epinephrine, norepinephrine, chromogranin and neuropeptides in response to various substances such as acetylcholine <ref name="PMID11215683"/>. [[File:ADRENAL MEDULLA .jpg|600px|thumb|right|Adrenal Medulla Histology]]<br /> <br /> There are many types of highly differentiated cells in the adult adrenal medulla: <br /> - Epinephrine cells (90% of all chromaffin cells) {{#pmid:24715564|PMID24715564}}<br /> - Norepinephrine cells (10% of all chromaffin cells) <ref name="PMID24715564"/><br /> - Small granule-containing cells (SGCs) <ref name="PMID11215683"/><br /> <br /> These cells also synthesise, store and secrete catecholamines through controlled and regulated pathways <ref name="PMID24715564"/>, such as various peptides like substance P and neurotensin.These cells have unique neuroendocrine characteristics as a result of their neural-crest origin. They receive preganglionic innervation by thoracic splanchnic nerves, and could almost be considered a specialised sympathetic ganglion. With postganglgionic bodies, cells of the medulla are densely clustered around their vasculature for the secretion of hormones into the bloodstream to moderate the concentration of epinephrine and norepinephrine. The adrenal medulla also contains presynaptic sympathetic ganglion cells <ref name="PMID11215683"/>. The small granule-containing cells are usually found in clusters whereas, the ganglion cells are found either individually or in clusters, usually dispersed among the chromaffin cells or among the nerve fibres {{#pmid:18021328|PMID18021328}}. During embryonic development (around weeks 9-12), in contrast to the developing adrenal cortex, the medulla does not show evidence of an organised structure other than a small cluster of cells scattered throughout its cortex {{#pmid:30247985|PMID30247985}}. <br /> <br /> <br /> <br /> ====Related Anatomy====<br /> <br /> The tissue and organ structure of the adrenal medulla should be understood with regard to its specialised function within the sympathetic nervous system. <br /> <br /> The medullary region of the adrenal glands is tasked with the endocrine secretions of adrenaline and nor-adrenaline in response to environmental stressors that are signalled for by the sympathetic nervous system. That is, the secretion of fight-or-flight response hormones in order to restrict vasculature to the trunk and increase vascular activity in the peripheral musculature.<br /> <br /> The adrenal glands are supplied by several branches of the great vessels in the abdominal cavity. The secreted catecholamines in the medulla are directly able to pass to the blood stream this way.<br /> <br /> These adrenal glands and their contents are retroperitoneal in the adult and varied in shape, with the left often being semilunar and right being pyramidal. Nervous supply of the adrenal glands is achieved by contributions from the splanchnic nerves of the celiac plexus. {{#pmid:11215683|PMID11215683}} <br /> <br /> [[File:Dd.jpg|400px|thumb|right|Adult Adrenal Glands in situ]] <br /> ----<br /> ====Role of the Adrenal Medulla====<br /> <br /> Understanding the biochemistry of catecholamines is necessary to see how the adrenal medulla is designed in the stages of embryology and how it is suited for life in the neonate and adult. <br /> <br /> The epinephrine and norepinephrine in the neonate and adult work by primarily changing the osmoregulatory state of vasculature in organs. With the exclusion of their neuromodulatory and neurotransmitter functions, epinephrine and norepinephrine are mainly tasked with the control of sympathetic and parasympathetic supplies. <br /> <br /> Norepinephrine is a constrictor of peripheral vasculature by antagonising the action of surface receptors expressed on the endothelium of blood vessels, specifically Alpha-1 and Alpha-2 receptors, such that vascular resistance increases. <br /> <br /> Epinephrine is both a vasoconstrictor and vasodilator, depending on what receptors it attaches to. As a non-selective adrenergic agonist, it acts on Alpha-1, Alpha-2, Beta-1, Beta-2 and Beta-3 receptors that are found throughout the body's tissues, yielding many different physiological responses. {{#pmid:19396395|PMID19396395}}<br /> <br /> '''Adult Function'''<br /> <br /> While the adrenal cortex releases glucocorticoids in response to long term stress, the adrenal medulla releases its hormones in response to short-term, acute stress. The adrenal medulla contains the neuroendocrine chromaffin cells which are responsible for secreting adrenaline and noradrenaline. The function of these hormones is primarily to maintain the body’s homeostasis, especially of the internal organs, and to properly activate the autonomic stress response, more commonly known as the ‘fight or flight’ response {{#pmid:30237243|PMID30237243}}. Thus the function of the medulla includes signalling the liver and skeletal muscles to convert glycogen into glucose for increased energy. This results in increased blood glucose levels. These hormones also increase the heart rate, pulse and blood pressure in preparation for the fight or flight response. In addition to this, these hormones dilate the lung airways and prompt vasodilation to further increase oxygenation of important organs such as the lung, brain and heart. Vasoconstriction of blood vessels is also prompted to other less essential organs such as the bladder and the digestive system.<br /> <br /> Other effects also include pupil dilation, dry mouth and a loss in peripheral vision <ref name="PMID18021328"/>. Paramount to the correct response of chromaffin cells is the synaptic connection of the preganglionic cells which originate from the central nervous system and project axons into the adrenal medulla. While this is a very important relationship, the mechanisms of this remains unknown <ref name="PMID30237243"/>. In addition to the release of catecholamines, cells in the medulla also release peptides through the process of exocytosis from chromaffin granules, to help regulate blood pressure and regulation throughout the body. These peptides also regulate the release of adrenaline and noradrenaline, blood vessel contraction and the immune response <ref name="PMID18021328"/>. <br /> <br /> '''Embryonic function'''<br /> <br /> The current knowledge about the development of the adrenal gland is limited, with nearly all models being from animals, and very limited functional data available from human fetal adrenals <ref name="PMID30247985"/>. Thus for these reasons, there is scarce information available on the embryonic adrenal medullary functions. Nevertheless, there is accumulating evidence that the catecholamines in the fetal adrenal medulla plays an important role in the time of delivery by controlling thermogenesis and heart regulation {{#pmid:6998630|PMID6998630}}. <br /> <br /> The hormones released by the medulla during birth also play a key role for the newborn’s adaptation to extrauterine life. Despite the immaturity of the adrenal medulla at birth, it is known that respiratory, metabolic and cardiovascular changes during delivery are dependent on the adrenomedullary hormones {{#pmid:3280659|PMID3280659}}. Experimental data from human and animal fetal research shows that the fetal sympathoadrenal system, consisting of the adrenal medulla, sympathetic neurons and chromaffin tissue work together to maintain fetal homeostasis {{#pmid:6346884|PMID6346884}}. The adrenal medulla thus appears to provide vital physiological functions for fetal and neonatal survival, especially during birth. <br /> <br /> <br /> ----<br /> <br /> ===Molecular mechanisms/factors/genes===<br /> ----<br /> <br /> ====Genes and Transcription Factors Involved with the Adrenal Medulla's Development====<br /> <br /> The 'story' of the Adrenal Medulla's neural crest tissue begins at the process of neurulation, the formation of the neural tube from the folding neural plate, which is comprised of developing ectoderm which is opposite to the primitive streak. It is here that several key chemical players are at work. The classic interpretation of Sonic Hedgehog (Shh) and Wnt signalling pathways as the only mediators here, has been shown to be incorrect. Research has uncovered other signallers such as: <br /> <br /> *Bone-Morphogenic-Protein-4 (BMP4) for the regional expression of nervous system distinctions in the growing neural plate. This maintains two important embryonic trancription factors known as Paired-Box (PAX) Genes 3 and 7 which can allow for expression of neural crest markers HNK-1, SRY-Box (SOX) 8, 9 and 10 as the neural tube closes and the neural crest delaminates from the folding. {{#pmid:16688176|PMID16688176}} <br /> <br /> *Slug via Wnt signalling, this allows for the loosening of gap junctions in the extracellular matrix surrounding the newly-formed neural tube and trunk of the embryo. This extracellular matrix has chemo-attractant molecules<br /> <br /> [[File:Catecholamine_Synthesis.jpg|400px|thumb|right|Biochemical Cascade of Catecholamine Synthesis]]<br /> <br /> The importance of Somitogenesis and Neural Crest come to a head when neural crest cells must migrate anteriorly past somites 18 to 24 <br /> <br /> Members of the SOX gene family have multiple key contributors to Neural Crest in the Adrenal Medulla.<br /> <br /> <br /> Mouse models have demonstrated that SOX-10 knock-outs (mice whose DNA has been engineered to not express SOX-10) do not have an adrenal medulla. There has also been suggestion that SOX-8,9 and 10 are all strongly related to the migratory patterning of neural crest cells to the developing adrenal glands. {{#pmid:18272785|PMID18272785}}<br /> <br /> The TH gene (for Tyrosine Hydroxylase) encodes the aforementioned enzyme in the adrenal medulla and central nervous system. Tyrosine Hydroxylase is crucial in biochemical pathways and cascades for the synthesis of catecholamines and other CNS neurotransmitters. The conversion from L-Tyrosine to L-DOPA is dependent upon the catalytic action of Tyrosine Hydroxylase. From there, L-DOPA can make Dopamine and eventually Epinephrine and Norepinephrine as well. {{#pmid:19396395|PMID19396395}}<br /> <br /> ===Abnormalities/abnormal development===<br /> ----<br /> <br /> Abnormalities of the Adrenal Medulla are much less common than its mesoderm-derived shell of the Adrenal Gland. Three of the most notorious abnormalities of the Adrenal Medulla include:<br /> <br /> * Pheochromocytomas<br /> * Ganglioneuromas<br /> * Neuroblastomas<br /> <br /> <br /> Pheochromocytomas (PCCs) are variable neoplasias of the adrenal medulla's chromaffin cells. There are many classifications of PCCs, with autosomal-dominant germ-line mutations and heredities being one of the main causes. Familial pheochromocytoma-paraganglioma (PGL) syndromes exist, with PGL1 having mutations of the SDHD gene, PGL3 being mutated of the SDHC gene and PGL4 having mutation of the SDHB gene. These phenotypically present as extra-adrenal chromaffin bodies, malformation of the adrenal glands themselves, absence of chromaffin bodies and fluctuations in circulating catecholamines. {{#pmid:18021328|PMID18021328}}<br /> <br /> Ganglioneuromas (GNs) are classically-benign growths that are very rare and arise from neural crest tissue. They are not circumscribed to the adrenal medulla, but also are found in the sympathetic chain and trunk ganglia. As a result of their scarcity, not much is known about them other than a few aberrant genes and generic clinical presentations. ERBB3, the receptor tyrosine kinas is understood to be important in the development of GNs, as well as an extremely high prevalence of up-regulated GATA3. A key thing to note is also the '''lack''' of N-MYC expression in GNs, which is quite prominent in neuroblastomas and other neoplasias. {{#pmid:29085827|PMID29085827}} {{#pmid:23715162|PMID23715162}} <br /> <br /> Neuroblastomas (NBs) are a more aggressive form of cancer, derived from neuroblasts - the precursor cells to neurons. A rather common pediatric cancer, they are often in children who are in risk factor groups such as those with aforementioned familial cancer syndromes, neurofibromatosis-1. These tumours often present with extremely variable catecholamine concentrations, which has implications for blood pressure, heart contractility and much more. Urinary excretion of norepinephrine, homovanillic acid (HVA) and vanilmandelic acid (VMA) can be used to help diagnose a suspected lesion of the adrenal gland, as these chemicals are associated with altered chemical cascades that are suspicious of neuroblastic change. {{#pmid:16372223|PMID16372223}}<br /> <br /> <br /> Apart from these abnormalities, there are other pathologies that may be connected to the adrenal medulla. One such example is a pathology of the Organ of Zuckerkandl. Also known as the para-aortic body, the Organ of Zuckerkandl is a primarily-gestational organ comprised of chromaffin cells and serves a similar purpose to the adrenal medulla in neonatal life.<br /> <br /> ===Animal models===<br /> ----<br /> Animal models are an integral part of research in embryology. In particular due to the moral concerns regarding the use of humans in scientific research. As a result different animals are used as substitutes to simulate the same environments and hope to achieve results that would also be able to represent humans as well. Prenatal adrenal gland development has been described in a number of scientific reports dating from the 1900s to studies in more recent years. These involved a variety of animal models such as ox, sheep, swine and most commonly mice. <br /> <br /> ====Chromaffin cells====<br /> There has been extensive research conducted into the adrenal chromaffin cells and their embryological developments. As explained above nueral crest cells are pluripotent meaning they are able to differentiate into multiple different cells{{#pmid:19377845|PMID19377845}}. The neural crest cells give rise to chromaffin cells of the adrenal medulla.<br /> <br /> =====Rat Models=====<br /> [[File:Adrenal gland.png|300px|thumb|right|3D images showing TH - positive cells accumulating at the cranial and audal ends of the adrenal gland. A. A observation of adrenal gland and surrounding structures (at 17 days of gestation). B. Enhanced image to further focus on the dark TH - positive cells. C. Image with the other structures removed.]]<br /> Previous research has reported that nueral crest cells differentiate into chromaffin cells around 19 days of gestation before forming the adrenal medulla{{#pmid:28684471|PMID2868441}}. Past research had also suggested that neural crest derived adrenal gland cells migrate using the sympathetic ganglia to the adrenal gland or preaortic ganglion, following different pathways, to reach their specific destination. However the results have shown that the pathways used to reach its destinations overlapped. This would suggest that there is a possibility of the cells using the same pathway to move from the beginning production to the destination that is the adrenal medulla (for chromaffin cells) and the preaortic ganglion (other cells involved in the sympathetic system). <br /> <br /> One particular study done by M.Yamato in 2004, along with his fellow scientists attempted to study the migration of neural crest cells in Wistar rats. In order to observe the formation adrenal medulla from the neural crest cells during the embryonic period, Yamato used anti - tyrosine hydroxylase (TH) antiserum injected into the rat embryos between 13-17 days of gestation. The anti - TH antiserum stain allows the scientists to visualize the neural crest cells under a light microscope. Later three dimensional images were created. From the images observed between 13 to 15 days of gestation, the TH - positive cells can be seen to move from the dorsal to the adrenal primordium{{#pmid:15240937|PMID15240937}}. After 16 days it was observed that a capsule had formed in some parts and TH - positive cells had penetrated the adrenal gland{{#pmid:15240937|PMID15240937}}. At seventeen days, TH - positive cells can be seen collecting at the medial part of the adrenal gland. The reconstructed images also shows that at the later stages during the 16-17 days of gestation, the accumulation of TH - positive cells grow and in combination with cell division leads to the formation of the adrenal medulla.<br /> <br /> =====Chicken models=====<br /> Chicken and rat models are often the most commonly used models when dealing with neural crest cells. In this particular review, collates multiple researchers results and presents evidence to discuss previous information suggesting that sympathetic neurons and chromaffin cells do not share a common progenitor{{#pmid:3693940|PMID3693940}}. The relevant study involved the use of cell cultures, Sympathoadrneal (SA) progenitor cells from embryonic(from chick embryos) and eary developmental stages were able to be procured. From these cultures it was easy to identify that glucocorticoids were crucial in the differentiation of SA cells into their derivatives, sympathetic neurons and chromaffin cells.<br /> <br /> [[File:Expression of BMP protein 4 .jpg|300px|thumb|right|Expression of BMP - 4 in the adrenal cortex at developmental stages. Shows the movement of the chromaffin progenitors moving from each stage of development. A-D: collection of progenitors outside E-H: cells have begun to penetrate the adrenal cortical region I-L: chromaffin cells have completely intergrated intergreted within the gland sg: sympathetic ganglia ac:adrenal cortical region ag: adrenal gland da: dorsal aortic region]]<br /> <br /> Another study conducted deals with the role of the bone morphogenetic protein(BMP-4) and its importance in the development of the adrenal medullary cells, chromaffin cells{{#pmid:18945349|PMID18945349}}. Previous research had shown that BMP - 4 a growth factor is plays an important role in the regulation of chromaffin cell production{{#pmid:10679774|PMID10679774}}. The researchers incubated chick embryos for 3 - 9 embryonic days and dissected them to be used for tissue cultures. Embryonic day 8 chick embryos had BMP - 4 overexpressing cells implanted in the sympathetic ganglia area, as well as other neurons which contained chromaffin like cells. What was observed was an increase in size and numbers of 'chromaffin' granules{{#pmid:18945349|PMID18945349}}. As a result it was concluded that although BMP - 4 promotes certain chromaffin traits, it does not have the capability to convert sympathetic neurons into a chromaffin type cell.<br /> <br /> ===Current research (labs)===<br /> ----<br /> <br /> ==== Generation of Adrenal Chromaffin-like Cells from Human Pluripotent Stem Cells====<br /> <br /> As explained above the adrenal medulla plays an important part in the autonomic system of an adult human. The chromaffin cells, in particular, are important neural crest derived cell that is closely related to the adrenal medulla. Previous findings have focused specifically on the mechanisms controlling the NCC migration and how these cells go on to form the different derivatives in their particular destinations in the embryo. For example, as previously explained studies have shown that chromaffin cells have been observed to move to the adrenal gland to form the medulla of the adrenal gland. This report goes through a recent study that involves the adrenal medullary cells, in particular chromaffin cells, and their potential to be used to model certain pathological diseases related to these cells. This is part of a study that also involves neural crest cells and their ability to differentiate into multiple different types of cells<ref>Lumb, R., & Schwarz, Q. (2015). Sympathoadrenal neural crest cells: The known, unknown and forgotten?. Development, Growth & Differentiation, 57(2), 146-157. doi: 10.1111/dgd.12189</ref>. Neural crest cells and SAPs from human embryonic cells and induced pluripotent stem cells were generated to be used in the experiment. By exposing the pluripotent stem cells to BMP4 in vitro, results showed that these cells would 'upregulate' the chromaffin cell - specific marker PMNT (an enzyme that synthesizes adrenaline). Furthermore when the cells from human embryos were implanted into avian embryos, there was a visible potential for the human cells to differentiate into cells that expressed the chromaffin cell markers{{#pmid:5768882|PMID5768882}}.<br /> <br /> <br /> ====Multipotent Peripheral Glial Cells Generate Neuroendocrine Cells of the Adrenal Medulla====<br /> <br /> Similar to the first study, this one also focuses on the chromaffin cells and their relationship to the adrenal medulla. Chromaffin cells often represent the main endocrine component that is believed to differentiate from neural crest cells{{#pmid:28684471|PMID28684471}}. The study focuses specifically on the idea that previous research has suggested that nerve - associated schwann cell precursor is a progenitor of chromaffin cells. What the findings suggested was that peripheral nerves provided migration routes for the progenitors. This is backed up by the results, a high concentration of chromaffin cells can be found being derived from the nerve, as nerve ablated mice in the experiment showed a large difference of 78% less cells compared to the control. Other than this, the study also brought to light the proliferative potential of the cells from nerves, with different other cell types being discovered as well (including cells such as parasympathetic{{#pmid:24925912|PMID24925912}} and melanocytes {{#pmid:19837037 |PMID19837037}}). The findings would provide useful information into further understanding the adrenal gland and its embryonic origins (as there is still much to learn regarding the formation of the adrenal medulla) but also pathological diseases such as neuroblastoma and pheochromatocytoma which are most common in the adrenal glandular region {{#pmid:23106811|PMID23106811}}.<br /> <br /> ===Glossary===<br /> ----<br /> *BMP4 - Bone Morphogenic Protein 4<br /> *DOPA - Dihydroxyphenylalanine<br /> *GATA3 - Transcription factor 3 for GATA gene<br /> *GN - Ganglioneuroma<br /> *GRN - Gene Regulatory Network<br /> *HNK1 - Human Natural Killer 1<br /> *HVA - Homovanillic Acid<br /> *L-DOPA - L-3,4-dihydroxyphenylalanine<br /> *NB - Neuroblastoma<br /> *PAX - Paired Box<br /> *PCC - Pheochromocytoma<br /> *PGL - Pheochromocytoma Paraganglioma<br /> *SGC - Small Granule Containing cells<br /> *SOX - Sry Box<br /> *TH - Tyrosine Hydroxylase<br /> *VMA -Vanilmandelic Acid<br /> <br /> ===Reference list===</div>

Z5091101 https://embryology.med.unsw.edu.au/embryology/index.php?title=2018_Group_Project_1&diff=358519 2018 Group Project 1 2018-10-16T07:26:51Z

<p>Z5091101: /* History */</p> <hr /> <div>=The Contribution of Neural Crest Cells to the Adrenal Medulla=<br /> ----<br /> {{2018ANAT2341ProjectHeader}}<br /> <br /> <br /> ===Introduction===<br /> <br /> ----<br /> <br /> The neural crest of an embryo migrates and differentiates to form various components of the body. This transient population of pluripotent stem-cells give rise to many complex and different structures across the adult by chemical signalling. One of these tissues is the medulla of the adrenal gland which is involved in the production of epinephrine and norepinephrine. This project will comprehensively outline the history of neural crest research, the embryonic developmental time course, tissue and organ structure, molecular mechanisms, abnormalities, animal models and current research.<br /> <br /> ===History===<br /> ----<br /> '''Describing the neural crest'''<br /> [[File:Wilhelm_His_History_Wilhelm.jpeg|left|230px|thumb|Wilhelm His]]<br /> [[File:NC Location.jpg|right|450px|thumb|The neural crest]]<br /> The "neural crest" is a structure in the embryo and is the junction between the neural and epidermal ectoderm. It is exclusive to vertebrates and forms a range of structures{{#pmid:22230617|PMID22230617}}. The neural crest contributes a large number of cells of varying structure and function that directly or indirectly contribute to the development of tissues and organs within the body {{#pmid:19179766|PMID19179766}}. In 1868, the neural crest cells were first identified in a chick embryo as a collection of cells known as "Zwischenstrang" by Professor Wilhelm His {{#pmid:22820859|PMID22820859}}. Wilhelm His was among the first to provide an explanation for the mechanics governing the developing embryo as well as the physiology and the organs that the differing germinal regions would eventually give rise to {{#pmid:19179766|PMID19179766}} This was due to his work in creating one of the first microtomes, a device that enables thin slicing of tissue. This enabled him to see embryonic tissues at greater magnifications and resolutions and gave the neural crest the name, the ganglionic crest {{#pmid:26970616|PMID26970616}}. In 1878, the term neural ridge was used to describe this collection of cells but the term neural crest was later coined by Arthur Milnes Marshall in 1879 in a paper he worked on disseminating the knowledge from his research on the development of cranial nerves in chicken embryos. {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1890s-1950s'''<br /> The neural crest is the point of origin for spinal/cranial ganglia and neurons. This theory received little criticism and was not contested much by other researchers prior to the 1890s. This is owing to the fact that the neural crest is quite closely related to the neural tube and thus this relationship makes sense. This discovery was made by His and Marshall, however, they found this out independently of one another.In the 1890s, Julia Platt, claimed that odontoblasts as well as the cartilages forming the facial and pharyngeal arch skeletons came from the ectoderm. This created much debate and was contested by many{{#pmid:22820859|PMID22820859}}. <br /> <br /> This is because this theory completely contradicted the germ-layer theory, whereby skeletal tissues originate at the mesoderm and not the ectoderm. The controversies this finding created brought about a slowing down of research, as demonstrated by a gap of almost 40 years between the theory that skeletal tissues originating from the neural crest. Today, it is known that the neural crest does indeed play a role in the development of the skeleton in vertebrates, particularly, the cranial neural crest. Although these studies were occurring, the focus was still primarily on researching pigment cells and ganglia of the spine up until the 1950s, when Sven Hörstadius' major work on the neural crest was published, titled "The Neural Crest: Its properties and derivatives in the light of experimental research". This work focused on experimental data tracing the development of the cartilaginous skeleton derived from the neural crest {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1960s - 1970s'''<br /> In the 1960s, the migration patterns of neural crest cells were studied in avian embryos (birds). This was a shift from studying the embryos of amphibians. This was inspired by studies conducted in the 1960s on neural crest cells migrating from the brain and spinal cord, known as trunk and cranial neural crest cells {{#pmid:19179766|PMID19179766}}. The cranial neural crest eventually becomes the bones, cartilage and connective tissues forming the foundation of the face, ears and teeth. The trunk neural crest cells can either become melanocytes or can migrate into sclerotomes which are later contributors to the cartilage of the spine and the dorsal root ganglia {{#pmid:22820859|PMID22820859}}. The cells in the trunk neural crest that migrate vertically become the sympathetic ganglia, the nerves proximal to the aorta and the adrenal medulla <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. In the 1970s many detailed maps signifying the pathways of many of the neural crest cells appeared as well as an understanding that the environment in which the neural crest cells are found plays a major role in their final development as well as the occurrences of abnormalities in the fetus {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1980s - 21st century'''<br /> [[File:Regions_of_NC_Cells.jpg|left|Neural crest regions|thumb|465px]]<br /> From the 1980s-1990s, the causative agent of organ transformation from one to another (homeotic patterning), as well as the Hox genes which regulate the axis of most symmetrical animal embryos were founded and studied. The neural crest, which previously was divided into the cranial and trunk regions, was now further divided into the vagal and sacral neural crest, the cardiac neural crest and the cephalic neural crest {{#pmid:19179766|PMID19179766}}. The vagal & sacral neural crest gives rise to the parasympathetic ganglia found in the gut. Without these ganglia, peristalsis, is not possible <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. The cardiac neural crest contributes to the valves, septa and major blood vessels of the heart, as well as connective tissues and cartilage{{#pmid:19179766|PMID19179766}}. This is important for the structure of the heart as well as its overall function, enabling it to move blood around the body efficiently as well as keep pulmonary and aortic circulation separated <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> <br /> <br /> Today, knowledge of the neural crest cells, their migration patterns, modes of differentiation, derivatives and apoptosis (cell death) are being studied extensively. This is being done on a comparative basis between different organisms, to add further evidence for evolution {{#pmid:19179766|PMID19179766}}. The neural crest is definitely forging a "crest" between the fields of developmental and evolutionary biology, as it is a structure '''shared exclusively by all vertebrates'''. Invertebrates do not derive their specialised cells from the neural crest as they do not have one, rather, they derive these from the endomesoderm {{#pmid:22230617|PMID22230617}}.<br /> <br /> '''Future directions'''<br /> <br /> Since its discovery by His, the neural crest field has made great progress, from studies performed on the structure, to analysis of the molecules and whether certain aspects of the neural crest are specific to a single species of organism, or to all vertebrates collectively. Future work on the cranial neural crest needs to be done as well as identifying and categorising the networks responsible for the proliferation and death of cells, as well as how the cells move and migrate, as well as the gene regulatory networks (GRNs) that regulate the synthesis of proteins. Advances in technology will undeniably lead us to more answers on the subject {{#pmid:22230617|PMID22230617}}.<br /> <br /> ===Developmental time course===<br /> ---- <br /> <br /> [[File:Adrenal_Medulla_Developmental_Timeline.jpg|right|thumb|500px]]<br /> <br /> The adrenal gland has two distinct sections, the cortex and the medulla, both with different embryonic origins. The cortex accounts for 90% of the adrenal glands and arises from intermediate mesoderm. The medulla only accounts for 10% of the adult adrenal glands, however it has neural crest embryonic origin. The medulla consists of chromaffinoblast cells which are migrant neuroblast cells from the neural crest, therefore the adrenal medulla is a component of the sympathetic nervous system.{{#pmid:21175739|PMID21175739}} Neural crest cells replicate in week 7 and begin to differentiate in week 8, the cells then migrate to the developing adrenal gland in week 9 of development.{{#pmid:25255746|PMID25255746}}{{#pmid:18279781|PMID18279781}} The neural crest cells infiltrate the cortex and the chromaffin cells are scattered islands in the cortex.{{#pmid:23354096|PMID23354096}} Throughout development the cells will become more compact in the centre of the gland, during this period of development the adrenal gland is growing rapidly. The gland is abnormally large until the second trimester and the medulla is much thicker prenatally.{{#pmid:18279781|PMID18279781}}{{#pmid:21175739|PMID21175739}}<br /> <br /> <br /> ===Embryonic origins===<br /> ----<br /> [[File:Trunk_NCC_migration.jpg|left|450px|thumb|Trunk NCC migration]]<br /> The adrenal gland is made up of the adrenal cortex and adrenal medulla, which both have different embryonic origins. The adrenal medulla arises from the neural crest tissue, found near the level of the coeliac plexus & sympathetic ganglion at somites 18-24 {{#pmid:16124976|PMID16124976}}. Specifically, this neural crest tissue comes from the trunk neural crest cells (see above figure to determine the approximate location in an embryo) <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> The trunk neural crest coordinates the development of the endocrine system, secretory cells, the peripheral nervous system and, to some degree, skeletal development, as well as innervation of the intestine {{#pmid: 28287247|PMID 28287247}}. The trunk neural cells arise caudally, undergo an epithelial to mesenchymal transition and follow three migratory pathways {{#pmid:20399766|PMID20399766}}.<br /> [[File:Differentiation_of_NCC.jpg|left|580px|thumb|Differentiation of chromaffin cells]]<br /> - A dorsolateral pathway (between ectoderm and somites), these become melanocytes, travel up to the point of the dermis and become a major part of the hair follicles and skin <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> - A ventrolateral pathway (through the somites)<br /> - A ventromedial pathway (between neural tube and posterior schlerotome){{#pmid:20399766|PMID20399766}}.<br /> <br /> Migration of neural crest cells from the sympathetic ganglion is what leads to the development of the adrenal medulla. In week 8 of development, immature cells called neuroblasts migrate through to the inner portion of the medulla, where they become the adrenal medulla {{#pmid:19683477|PMID19683477}}. Chromaffin cells are neuroendocrine cells and are found in the sympathetic ganglia and make up the majority of the adrenal medulla{{#pmid:19683477|PMID19683477}}. They synthesise and release a range of hormones in the body and arise from the temporary neural crest. The term chromaffin was inspired by the staining capacity of these cells when they came into contact with chrome salts. They make, store, export and use catecholamines, responsible for making noradrenaline and originate at the caudal region of somites 18-24 of the neural crest, also known as the adrenomedullary region {{#pmid:19683477|PMID19683477}}.<br /> <br /> For cells to leave the neural crest and begin their migration, certain conditions need to be met, that is, the cells need to be loosely connected, their tight junctions becoming relaxed, initiated by "Slug protein" and a loss of N-Cadherin which also leads to the loosening of these junctions. The surrounding matrix as well as chemotactic and stem cell factors of the neural tube are then what dictates how the neural crest cells move, some proteins stopping their migration to that area and others encouraging the movement <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. After splitting apart, the first neural crest cells move ventrally and pass into the spaces between the somites and then, through the anterior portions of each segment until they arrive at the para-aortic sites, where they become the cells of the sympathetic ganglia and the adrenal medulla {{#pmid:19683477|PMID19683477}}. BMP-4 (bone morphogenetic protein 4) then acts on these neural crest cells, preventing them from becoming cells that have a neural function and causing them to become chromaffin cells at the adrenal medulla. Glucocorticoids then play a role in maintenance of chromaffin cells in postnatal life, this was only found recently, as previously it was thought that glucocorticoids were responsible entirely for the differentiation of neural crest cells into chromaffin, or adrenomedullary cells {{#pmid:23220335|PMID23220335}}.<br /> <br /> ===Anatomy and Functions===<br /> <br /> ----<br /> <br /> ====Anatomy and Histology====<br /> <br /> The adrenal medulla makes up the inner section of the adrenal glands, and is surrounded by the cortex, and a connective tissue capsule. It lies in the centre of the gland and it rarely measures no more than 2mm in thickness {{#pmid:21107679|PMID21107679}}. The cells of the adrenal medulla are derived from the neural crest as opposed to the mesodermal origins of the cortex. The adrenal medulla contains secretory cells called chromaffin cells due to the agents they produce when oxidised, such as chromate {{#pmid:11215683|PMID11215683}}. These cells secrete epinephrine, norepinephrine, chromogranin and neuropeptides in response to various substances such as acetylcholine <ref name="PMID11215683"/>. [[File:ADRENAL MEDULLA .jpg|600px|thumb|right|Adrenal Medulla Histology]]<br /> <br /> There are many types of highly differentiated cells in the adult adrenal medulla: <br /> - Epinephrine cells (90% of all chromaffin cells) {{#pmid:24715564|PMID24715564}}<br /> - Norepinephrine cells (10% of all chromaffin cells) <ref name="PMID24715564"/><br /> - Small granule-containing cells (SGCs) <ref name="PMID11215683"/><br /> <br /> These cells also synthesise, store and secrete catecholamines through controlled and regulated pathways <ref name="PMID24715564"/>, such as various peptides like substance P and neurotensin.These cells have unique neuroendocrine characteristics as a result of their neural-crest origin. They receive preganglionic innervation by thoracic splanchnic nerves, and could almost be considered a specialised sympathetic ganglion. With postganglgionic bodies, cells of the medulla are densely clustered around their vasculature for the secretion of hormones into the bloodstream to moderate the concentration of epinephrine and norepinephrine. The adrenal medulla also contains presynaptic sympathetic ganglion cells <ref name="PMID11215683"/>. The small granule-containing cells are usually found in clusters whereas, the ganglion cells are found either individually or in clusters, usually dispersed among the chromaffin cells or among the nerve fibres {{#pmid:18021328|PMID18021328}}. During embryonic development (around weeks 9-12), in contrast to the developing adrenal cortex, the medulla does not show evidence of an organised structure other than a small cluster of cells scattered throughout its cortex {{#pmid:30247985|PMID30247985}}. <br /> <br /> <br /> <br /> ====Related Anatomy====<br /> <br /> The tissue and organ structure of the adrenal medulla should be understood with regard to its specialised function within the sympathetic nervous system. <br /> <br /> The medullary region of the adrenal glands is tasked with the endocrine secretions of adrenaline and nor-adrenaline in response to environmental stressors that are signalled for by the sympathetic nervous system. That is, the secretion of fight-or-flight response hormones in order to restrict vasculature to the trunk and increase vascular activity in the peripheral musculature.<br /> <br /> The adrenal glands are supplied by several branches of the great vessels in the abdominal cavity. The secreted catecholamines in the medulla are directly able to pass to the blood stream this way.<br /> <br /> These adrenal glands and their contents are retroperitoneal in the adult and varied in shape, with the left often being semilunar and right being pyramidal. Nervous supply of the adrenal glands is achieved by contributions from the splanchnic nerves of the celiac plexus. {{#pmid:11215683|PMID11215683}} <br /> <br /> [[File:Dd.jpg|400px|thumb|right|Adult Adrenal Glands in situ]] <br /> ----<br /> ====Role of the Adrenal Medulla====<br /> <br /> Understanding the biochemistry of catecholamines is necessary to see how the adrenal medulla is designed in the stages of embryology and how it is suited for life in the neonate and adult. <br /> <br /> The epinephrine and norepinephrine in the neonate and adult work by primarily changing the osmoregulatory state of vasculature in organs. With the exclusion of their neuromodulatory and neurotransmitter functions, epinephrine and norepinephrine are mainly tasked with the control of sympathetic and parasympathetic supplies. <br /> <br /> Norepinephrine is a constrictor of peripheral vasculature by antagonising the action of surface receptors expressed on the endothelium of blood vessels, specifically Alpha-1 and Alpha-2 receptors, such that vascular resistance increases. <br /> <br /> Epinephrine is both a vasoconstrictor and vasodilator, depending on what receptors it attaches to. As a non-selective adrenergic agonist, it acts on Alpha-1, Alpha-2, Beta-1, Beta-2 and Beta-3 receptors that are found throughout the body's tissues, yielding many different physiological responses. {{#pmid:19396395|PMID19396395}}<br /> <br /> '''Adult Function'''<br /> <br /> While the adrenal cortex releases glucocorticoids in response to long term stress, the adrenal medulla releases its hormones in response to short-term, acute stress. The adrenal medulla contains the neuroendocrine chromaffin cells which are responsible for secreting adrenaline and noradrenaline. The function of these hormones is primarily to maintain the body’s homeostasis, especially of the internal organs, and to properly activate the autonomic stress response, more commonly known as the ‘fight or flight’ response {{#pmid:30237243|PMID30237243}}. Thus the function of the medulla includes signalling the liver and skeletal muscles to convert glycogen into glucose for increased energy. This results in increased blood glucose levels. These hormones also increase the heart rate, pulse and blood pressure in preparation for the fight or flight response. In addition to this, these hormones dilate the lung airways and prompt vasodilation to further increase oxygenation of important organs such as the lung, brain and heart. Vasoconstriction of blood vessels is also prompted to other less essential organs such as the bladder and the digestive system.<br /> <br /> Other effects also include pupil dilation, dry mouth and a loss in peripheral vision <ref name="PMID18021328"/>. Paramount to the correct response of chromaffin cells is the synaptic connection of the preganglionic cells which originate from the central nervous system and project axons into the adrenal medulla. While this is a very important relationship, the mechanisms of this remains unknown <ref name="PMID30237243"/>. In addition to the release of catecholamines, cells in the medulla also release peptides through the process of exocytosis from chromaffin granules, to help regulate blood pressure and regulation throughout the body. These peptides also regulate the release of adrenaline and noradrenaline, blood vessel contraction and the immune response <ref name="PMID18021328"/>. <br /> <br /> '''Embryonic function'''<br /> <br /> The current knowledge about the development of the adrenal gland is limited, with nearly all models being from animals, and very limited functional data available from human fetal adrenals <ref name="PMID30247985"/>. Thus for these reasons, there is scarce information available on the embryonic adrenal medullary functions. Nevertheless, there is accumulating evidence that the catecholamines in the fetal adrenal medulla plays an important role in the time of delivery by controlling thermogenesis and heart regulation {{#pmid:6998630|PMID6998630}}. <br /> <br /> The hormones released by the medulla during birth also play a key role for the newborn’s adaptation to extrauterine life. Despite the immaturity of the adrenal medulla at birth, it is known that respiratory, metabolic and cardiovascular changes during delivery are dependent on the adrenomedullary hormones {{#pmid:3280659|PMID3280659}}. Experimental data from human and animal fetal research shows that the fetal sympathoadrenal system, consisting of the adrenal medulla, sympathetic neurons and chromaffin tissue work together to maintain fetal homeostasis {{#pmid:6346884|PMID6346884}}. The adrenal medulla thus appears to provide vital physiological functions for fetal and neonatal survival, especially during birth. <br /> <br /> <br /> ----<br /> <br /> ===Molecular mechanisms/factors/genes===<br /> ----<br /> <br /> ====Genes and Transcription Factors Involved with the Adrenal Medulla's Development====<br /> <br /> The 'story' of the Adrenal Medulla's neural crest tissue begins at the process of neurulation, the formation of the neural tube from the folding neural plate, which is comprised of developing ectoderm which is opposite to the primitive streak. It is here that several key chemical players are at work. The classic interpretation of Sonic Hedgehog (Shh) and Wnt signalling pathways as the only mediators here, has been shown to be incorrect. Research has uncovered other signallers such as: <br /> <br /> *Bone-Morphogenic-Protein-4 (BMP4) for the regional expression of nervous system distinctions in the growing neural plate. This maintains two important embryonic trancription factors known as Paired-Box (PAX) Genes 3 and 7 which can allow for expression of neural crest markers HNK-1, SRY-Box (SOX) 8, 9 and 10 as the neural tube closes and the neural crest delaminates from the folding. {{#pmid:16688176|PMID16688176}} <br /> <br /> *Slug via Wnt signalling, this allows for the loosening of gap junctions in the extracellular matrix surrounding the newly-formed neural tube and trunk of the embryo. This extracellular matrix has chemo-attractant molecules<br /> <br /> [[File:Catecholamine_Synthesis.jpg|400px|thumb|right|Biochemical Cascade of Catecholamine Synthesis]]<br /> <br /> The importance of Somitogenesis and Neural Crest come to a head when neural crest cells must migrate anteriorly past somites 18 to 24 <br /> <br /> Members of the SOX gene family have multiple key contributors to Neural Crest in the Adrenal Medulla.<br /> <br /> <br /> Mouse models have demonstrated that SOX-10 knock-outs (mice whose DNA has been engineered to not express SOX-10) do not have an adrenal medulla. There has also been suggestion that SOX-8,9 and 10 are all strongly related to the migratory patterning of neural crest cells to the developing adrenal glands. {{#pmid:18272785|PMID18272785}}<br /> <br /> The TH gene (for Tyrosine Hydroxylase) encodes the aforementioned enzyme in the adrenal medulla and central nervous system. Tyrosine Hydroxylase is crucial in biochemical pathways and cascades for the synthesis of catecholamines and other CNS neurotransmitters. The conversion from L-Tyrosine to L-DOPA is dependent upon the catalytic action of Tyrosine Hydroxylase. From there, L-DOPA can make Dopamine and eventually Epinephrine and Norepinephrine as well. {{#pmid:19396395|PMID19396395}}<br /> <br /> ===Abnormalities/abnormal development===<br /> ----<br /> <br /> Abnormalities of the Adrenal Medulla are much less common than its mesoderm-derived shell of the Adrenal Gland. Three of the most notorious abnormalities of the Adrenal Medulla include:<br /> <br /> * Pheochromocytomas<br /> * Ganglioneuromas<br /> * Neuroblastomas<br /> <br /> <br /> Pheochromocytomas (PCCs) are variable neoplasias of the adrenal medulla's chromaffin cells. There are many classifications of PCCs, with autosomal-dominant germ-line mutations and heredities being one of the main causes. Familial pheochromocytoma-paraganglioma (PGL) syndromes exist, with PGL1 having mutations of the SDHD gene, PGL3 being mutated of the SDHC gene and PGL4 having mutation of the SDHB gene. These phenotypically present as extra-adrenal chromaffin bodies, malformation of the adrenal glands themselves, absence of chromaffin bodies and fluctuations in circulating catecholamines. {{#pmid:18021328|PMID18021328}}<br /> <br /> Ganglioneuromas (GNs) are classically-benign growths that are very rare and arise from neural crest tissue. They are not circumscribed to the adrenal medulla, but also are found in the sympathetic chain and trunk ganglia. As a result of their scarcity, not much is known about them other than a few aberrant genes and generic clinical presentations. ERBB3, the receptor tyrosine kinas is understood to be important in the development of GNs, as well as an extremely high prevalence of up-regulated GATA3. A key thing to note is also the '''lack''' of N-MYC expression in GNs, which is quite prominent in neuroblastomas and other neoplasias. {{#pmid:29085827|PMID29085827}} {{#pmid:23715162|PMID23715162}} <br /> <br /> Neuroblastomas (NBs) are a more aggressive form of cancer, derived from neuroblasts - the precursor cells to neurons. A rather common pediatric cancer, they are often in children who are in risk factor groups such as those with aforementioned familial cancer syndromes, neurofibromatosis-1. These tumours often present with extremely variable catecholamine concentrations, which has implications for blood pressure, heart contractility and much more. Urinary excretion of norepinephrine, homovanillic acid (HVA) and vanilmandelic acid (VMA) can be used to help diagnose a suspected lesion of the adrenal gland, as these chemicals are associated with altered chemical cascades that are suspicious of neuroblastic change. {{#pmid:16372223|PMID16372223}}<br /> <br /> <br /> Apart from these abnormalities, there are other pathologies that may be connected to the adrenal medulla. One such example is a pathology of the Organ of Zuckerkandl. Also known as the para-aortic body, the Organ of Zuckerkandl is a primarily-gestational organ comprised of chromaffin cells and serves a similar purpose to the adrenal medulla in neonatal life.<br /> <br /> ===Animal models===<br /> ----<br /> Animal models are an integral part of research in embryology. In particular due to the moral concerns regarding the use of humans in scientific research. As a result different animals are used as substitutes to simulate the same environments and hope to achieve results that would also be able to represent humans as well. Prenatal adrenal gland development has been described in a number of scientific reports dating from the 1900s to studies in more recent years. These involved a variety of animal models such as ox, sheep, swine and most commonly mice. <br /> <br /> ====Chromaffin cells====<br /> There has been extensive research conducted into the adrenal chromaffin cells and their embryological developments. As explained above nueral crest cells are pluripotent meaning they are able to differentiate into multiple different cells{{#pmid:19377845|PMID19377845}}. The neural crest cells give rise to chromaffin cells of the adrenal medulla.<br /> <br /> =====Rat Models=====<br /> [[File:Adrenal gland.png|300px|thumb|right|3D images showing TH - positive cells accumulating at the cranial and audal ends of the adrenal gland. A. A observation of adrenal gland and surrounding structures (at 17 days of gestation). B. Enhanced image to further focus on the dark TH - positive cells. C. Image with the other structures removed.]]<br /> Previous research has reported that nueral crest cells differentiate into chromaffin cells around 19 days of gestation before forming the adrenal medulla{{#pmid:28684471|PMID2868441}}. Past research had also suggested that neural crest derived adrenal gland cells migrate using the sympathetic ganglia to the adrenal gland or preaortic ganglion, following different pathways, to reach their specific destination. However the results have shown that the pathways used to reach its destinations overlapped. This would suggest that there is a possibility of the cells using the same pathway to move from the beginning production to the destination that is the adrenal medulla (for chromaffin cells) and the preaortic ganglion (other cells involved in the sympathetic system). <br /> <br /> One particular study done by M.Yamato in 2004, along with his fellow scientists attempted to study the migration of neural crest cells in Wistar rats. In order to observe the formation adrenal medulla from the neural crest cells during the embryonic period, Yamato used anti - tyrosine hydroxylase (TH) antiserum injected into the rat embryos between 13-17 days of gestation. The anti - TH antiserum stain allows the scientists to visualize the neural crest cells under a light microscope. Later three dimensional images were created. From the images observed between 13 to 15 days of gestation, the TH - positive cells can be seen to move from the dorsal to the adrenal primordium{{#pmid:15240937|PMID15240937}}. After 16 days it was observed that a capsule had formed in some parts and TH - positive cells had penetrated the adrenal gland{{#pmid:15240937|PMID15240937}}. At seventeen days, TH - positive cells can be seen collecting at the medial part of the adrenal gland. The reconstructed images also shows that at the later stages during the 16-17 days of gestation, the accumulation of TH - positive cells grow and in combination with cell division leads to the formation of the adrenal medulla.<br /> <br /> =====Chicken models=====<br /> Chicken and rat models are often the most commonly used models when dealing with neural crest cells. In this particular review, collates multiple researchers results and presents evidence to discuss previous information suggesting that sympathetic neurons and chromaffin cells do not share a common progenitor{{#pmid:3693940|PMID3693940}}. The relevant study involved the use of cell cultures, Sympathoadrneal (SA) progenitor cells from embryonic(from chick embryos) and eary developmental stages were able to be procured. From these cultures it was easy to identify that glucocorticoids were crucial in the differentiation of SA cells into their derivatives, sympathetic neurons and chromaffin cells.<br /> <br /> [[File:Expression of BMP protein 4 .jpg|300px|thumb|right|Expression of BMP - 4 in the adrenal cortex at developmental stages. Shows the movement of the chromaffin progenitors moving from each stage of development. A-D: collection of progenitors outside E-H: cells have begun to penetrate the adrenal cortical region I-L: chromaffin cells have completely intergrated intergreted within the gland sg: sympathetic ganglia ac:adrenal cortical region ag: adrenal gland da: dorsal aortic region]]<br /> <br /> Another study conducted deals with the role of the bone morphogenetic protein(BMP-4) and its importance in the development of the adrenal medullary cells, chromaffin cells{{#pmid:18945349|PMID18945349}}. Previous research had shown that BMP - 4 a growth factor is plays an important role in the regulation of chromaffin cell production{{#pmid:10679774|PMID10679774}}. The researchers incubated chick embryos for 3 - 9 embryonic days and dissected them to be used for tissue cultures. Embryonic day 8 chick embryos had BMP - 4 overexpressing cells implanted in the sympathetic ganglia area, as well as other neurons which contained chromaffin like cells. What was observed was an increase in size and numbers of 'chromaffin' granules{{#pmid:18945349|PMID18945349}}. As a result it was concluded that although BMP - 4 promotes certain chromaffin traits, it does not have the capability to convert sympathetic neurons into a chromaffin type cell.<br /> <br /> ===Current research (labs)===<br /> ----<br /> <br /> ==== Generation of Adrenal Chromaffin-like Cells from Human Pluripotent Stem Cells====<br /> <br /> As explained above the adrenal medulla plays an important part in the autonomic system of an adult human. The chromaffin cells, in particular, are important neural crest derived cell that is closely related to the adrenal medulla. Previous findings have focused specifically on the mechanisms controlling the NCC migration and how these cells go on to form the different derivatives in their particular destinations in the embryo. For example, as previously explained studies have shown that chromaffin cells have been observed to move to the adrenal gland to form the medulla of the adrenal gland. This report goes through a recent study that involves the adrenal medullary cells, in particular chromaffin cells, and their potential to be used to model certain pathological diseases related to these cells. This is part of a study that also involves neural crest cells and their ability to differentiate into multiple different types of cells<ref>Lumb, R., & Schwarz, Q. (2015). Sympathoadrenal neural crest cells: The known, unknown and forgotten?. Development, Growth & Differentiation, 57(2), 146-157. doi: 10.1111/dgd.12189</ref>. Neural crest cells and SAPs from human embryonic cells and induced pluripotent stem cells were generated to be used in the experiment. By exposing the pluripotent stem cells to BMP4 in vitro, results showed that these cells would 'upregulate' the chromaffin cell - specific marker PMNT (an enzyme that synthesizes adrenaline). Furthermore when the cells from human embryos were implanted into avian embryos, there was a visible potential for the human cells to differentiate into cells that expressed the chromaffin cell markers{{#pmid:5768882|PMID5768882}}.<br /> <br /> <br /> ====Multipotent Peripheral Glial Cells Generate Neuroendocrine Cells of the Adrenal Medulla====<br /> <br /> Similar to the first study, this one also focuses on the chromaffin cells and their relationship to the adrenal medulla. Chromaffin cells often represent the main endocrine component that is believed to differentiate from neural crest cells{{#pmid:28684471|PMID28684471}}. The study focuses specifically on the idea that previous research has suggested that nerve - associated schwann cell precursor is a progenitor of chromaffin cells. What the findings suggested was that peripheral nerves provided migration routes for the progenitors. This is backed up by the results, a high concentration of chromaffin cells can be found being derived from the nerve, as nerve ablated mice in the experiment showed a large difference of 78% less cells compared to the control. Other than this, the study also brought to light the proliferative potential of the cells from nerves, with different other cell types being discovered as well (including cells such as parasympathetic{{#pmid:24925912|PMID24925912}} and melanocytes {{#pmid:19837037 |PMID19837037}}). The findings would provide useful information into further understanding the adrenal gland and its embryonic origins (as there is still much to learn regarding the formation of the adrenal medulla) but also pathological diseases such as neuroblastoma and pheochromatocytoma which are most common in the adrenal glandular region {{#pmid:23106811|PMID23106811}}.<br /> <br /> ===Glossary===<br /> ----<br /> *BMP4 - Bone Morphogenic Protein 4<br /> *DOPA - Dihydroxyphenylalanine<br /> *GATA3 - Transcription factor 3 for GATA gene<br /> *GN - Ganglioneuroma<br /> *GRN - Gene Regulatory Network<br /> *HNK1 - Human Natural Killer 1<br /> *HVA - Homovanillic Acid<br /> *L-DOPA - L-3,4-dihydroxyphenylalanine<br /> *NB - Neuroblastoma<br /> *PAX - Paired Box<br /> *PCC - Pheochromocytoma<br /> *PGL - Pheochromocytoma Paraganglioma<br /> *SGC - Small Granule Containing cells<br /> *SOX - Sry Box<br /> *TH - Tyrosine Hydroxylase<br /> *VMA -Vanilmandelic Acid<br /> <br /> ===Reference list===</div>

Z5091101 https://embryology.med.unsw.edu.au/embryology/index.php?title=2018_Group_Project_1&diff=358301 2018 Group Project 1 2018-10-16T00:39:57Z

<p>Z5091101: /* History */</p> <hr /> <div>=The Contribution of Neural Crest Cells to the Adrenal Medulla=<br /> ----<br /> {{2018ANAT2341ProjectHeader}}<br /> <br /> <br /> ===Introduction===<br /> <br /> ----<br /> <br /> The neural crest of an embryo migrates and differentiates to form various components of the body. This transient population of pluripotent stem-cells give rise to many complex and different structures across the adult by chemical signalling. One of these tissues is the medulla of the adrenal gland which is involved in the production of epinephrine and norepinephrine. This project will comprehensively outline the history of neural crest research, the embryonic developmental time course, tissue and organ structure, molecular mechanisms, abnormalities, animal models and current research.<br /> <br /> ===History===<br /> ----<br /> '''Describing the neural crest'''<br /> [[File:Wilhelm_His_History_Wilhelm.jpeg|left|230px|thumb|Wilhelm His]]<br /> [[File:NC Location.jpg|right|450px|thumb|The neural crest]]<br /> The "neural crest" is a structure in the embryo and is the junction between the neural and epidermal ectoderm. It is exclusive to vertebrates and forms a range of structures{{#pmid:22230617|PMID22230617}}. The neural crest contributes a large number of cells of varying structure and function that directly or indirectly contribute to the development of tissues and organs within the body {{#pmid:19179766|PMID19179766}}. In 1868, the neural crest cells were first identified in a chick embryo as a collection of cells known as "Zwischenstrang" by Professor Wilhelm His {{#pmid:22820859|PMID22820859}}. Wilhelm His was among the first to provide an explanation for the mechanics governing the developing embryo as well as the physiology and the organs that the differing germinal regions would eventually give rise to. In 1878, the term neural ridge was used to describe this collection of cells but the term neural crest was later coined by Arthur Milnes Marshall in 1879 in a paper he worked on disseminating the knowledge from his research on the development of cranial nerves in chicken embryos. {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1890s-1950s'''<br /> The neural crest is the point of origin for spinal/cranial ganglia and neurons. This theory received little criticism and was not contested much by other researchers prior to the 1890s. This is owing to the fact that the neural crest is quite closely related to the neural tube and thus this relationship makes sense. This discovery was made by His and Marshall, however, they found this out independently of one another.In the 1890s, Julia Platt, claimed that odontoblasts as well as the cartilages forming the facial and pharyngeal arch skeletons came from the ectoderm. This created much debate and was contested by many{{#pmid:22820859|PMID22820859}}. <br /> <br /> This is because this theory completely contradicted the germ-layer theory, whereby skeletal tissues originate at the mesoderm and not the ectoderm. The controversies this finding created brought about a slowing down of research, as demonstrated by a gap of almost 40 years between the theory that skeletal tissues originating from the neural crest. Today, it is known that the neural crest does indeed play a role in the development of the skeleton in vertebrates, particularly, the cranial neural crest. Although these studies were occurring, the focus was still primarily on researching pigment cells and ganglia of the spine up until the 1950s, when Sven Hörstadius' major work on the neural crest was published, titled "The Neural Crest: Its properties and derivatives in the light of experimental research". This work focused on experimental data tracing the development of the cartilaginous skeleton derived from the neural crest {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1960s - 1970s'''<br /> In the 1960s, the migration patterns of neural crest cells were studied in avian embryos (birds). This was a shift from studying the embryos of amphibians. This was inspired by studies conducted in the 1960s on neural crest cells migrating from the brain and spinal cord, known as trunk and cranial neural crest cells {{#pmid:19179766|PMID19179766}}. The cranial neural crest eventually becomes the bones, cartilage and connective tissues forming the foundation of the face, ears and teeth. The trunk neural crest cells can either become melanocytes or can migrate into sclerotomes which are later contributors to the cartilage of the spine and the dorsal root ganglia {{#pmid:22820859|PMID22820859}}. The cells in the trunk neural crest that migrate vertically become the sympathetic ganglia, the nerves proximal to the aorta and the adrenal medulla <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. In the 1970s many detailed maps signifying the pathways of many of the neural crest cells appeared as well as an understanding that the environment in which the neural crest cells are found plays a major role in their final development as well as the occurrences of abnormalities in the fetus {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1980s - 21st century'''<br /> [[File:Regions_of_NC_Cells.jpg|left|Neural crest regions|thumb|465px]]<br /> From the 1980s-1990s, the causative agent of organ transformation from one to another (homeotic patterning), as well as the Hox genes which regulate the axis of most symmetrical animal embryos were founded and studied. The neural crest, which previously was divided into the cranial and trunk regions, was now further divided into the vagal and sacral neural crest, the cardiac neural crest and the cephalic neural crest {{#pmid:19179766|PMID19179766}}. The vagal & sacral neural crest gives rise to the parasympathetic ganglia found in the gut. Without these ganglia, peristalsis, is not possible <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. The cardiac neural crest contributes to the valves, septa and major blood vessels of the heart, as well as connective tissues and cartilage{{#pmid:19179766|PMID19179766}}. This is important for the structure of the heart as well as its overall function, enabling it to move blood around the body efficiently as well as keep pulmonary and aortic circulation separated <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> <br /> <br /> Today, knowledge of the neural crest cells, their migration patterns, modes of differentiation, derivatives and apoptosis (cell death) are being studied extensively. This is being done on a comparative basis between different organisms, to add further evidence for evolution {{#pmid:19179766|PMID19179766}}. The neural crest is definitely forging a "crest" between the fields of developmental and evolutionary biology, as it is a structure '''shared exclusively by all vertebrates'''. Invertebrates do not derive their specialised cells from the neural crest as they do not have one, rather, they derive these from the endomesoderm {{#pmid:22230617|PMID22230617}}.<br /> <br /> '''Future directions'''<br /> <br /> Since its discovery by His, the neural crest field has made great progress, from studies performed on the structure, to analysis of the molecules and whether certain aspects of the neural crest are specific to a single species of organism, or to all vertebrates collectively. Future work on the cranial neural crest needs to be done as well as identifying and categorising the networks responsible for the proliferation and death of cells, as well as how the cells move and migrate, as well as the gene regulatory networks (GRNs) that regulate the synthesis of proteins. Advances in technology will undeniably lead us to more answers on the subject {{#pmid:22230617|PMID22230617}}.<br /> <br /> ===Developmental time course===<br /> ---- <br /> <br /> [[File:Adrenal_Medulla_Developmental_Timeline.jpg|right|thumb|500px]]<br /> <br /> The adrenal gland has two distinct sections, the cortex and the medulla, both with different embryonic origins. The cortex accounts for 90% of the adrenal glands and arises from intermediate mesoderm. The medulla only accounts for 10% of the adult adrenal glands, however it has neural crest embryonic origin. The medulla consists of chromaffinoblast cells which are migrant neuroblast cells from the neural crest, therefore the adrenal medulla is a component of the sympathetic nervous system.{{#pmid:21175739|PMID21175739}} Neural crest cells replicate in week 7 and begin to differentiate in week 8, the cells then migrate to the developing adrenal gland in week 9 of development.{{#pmid:25255746|PMID25255746}}{{#pmid:18279781|PMID18279781}} The neural crest cells infiltrate the cortex and the chromaffin cells are scattered islands in the cortex.{{#pmid:23354096|PMID23354096}} Throughout development the cells will become more compact in the centre of the gland, during this period of development the adrenal gland is growing rapidly. The gland is abnormally large until the second trimester and the medulla is much thicker prenatally.{{#pmid:18279781|PMID18279781}}{{#pmid:21175739|PMID21175739}}<br /> <br /> <br /> ===Embryonic origins===<br /> ----<br /> [[File:Trunk_NCC_migration.jpg|left|450px|thumb|Trunk NCC migration]]<br /> The adrenal gland is made up of the adrenal cortex and adrenal medulla, which both have different embryonic origins. The adrenal medulla arises from the neural crest tissue, found near the level of the coeliac plexus & sympathetic ganglion at somites 18-24 {{#pmid:16124976|PMID16124976}}. Specifically, this neural crest tissue comes from the trunk neural crest cells (see above figure to determine the approximate location in an embryo) <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> The trunk neural crest coordinates the development of the endocrine system, secretory cells, the peripheral nervous system and, to some degree, skeletal development, as well as innervation of the intestine {{#pmid: 28287247|PMID 28287247}}. The trunk neural cells arise caudally, undergo an epithelial to mesenchymal transition and follow three migratory pathways {{#pmid:20399766|PMID20399766}}.<br /> [[File:Differentiation_of_NCC.jpg|left|580px|thumb|Differentiation of chromaffin cells]]<br /> - A dorsolateral pathway (between ectoderm and somites), these become melanocytes, travel up to the point of the dermis and become a major part of the hair follicles and skin <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> - A ventrolateral pathway (through the somites)<br /> - A ventromedial pathway (between neural tube and posterior schlerotome){{#pmid:20399766|PMID20399766}}.<br /> <br /> Migration of neural crest cells from the sympathetic ganglion is what leads to the development of the adrenal medulla. In week 8 of development, immature cells called neuroblasts migrate through to the inner portion of the medulla, where they become the adrenal medulla {{#pmid:19683477|PMID19683477}}. Chromaffin cells are neuroendocrine cells and are found in the sympathetic ganglia and make up the majority of the adrenal medulla{{#pmid:19683477|PMID19683477}}. They synthesise and release a range of hormones in the body and arise from the temporary neural crest. The term chromaffin was inspired by the staining capacity of these cells when they came into contact with chrome salts. They make, store, export and use catecholamines, responsible for making noradrenaline and originate at the caudal region of somites 18-24 of the neural crest, also known as the adrenomedullary region {{#pmid:19683477|PMID19683477}}.<br /> <br /> For cells to leave the neural crest and begin their migration, certain conditions need to be met, that is, the cells need to be loosely connected, their tight junctions becoming relaxed, initiated by "Slug protein" and a loss of N-Cadherin which also leads to the loosening of these junctions. The surrounding matrix as well as chemotactic and stem cell factors of the neural tube are then what dictates how the neural crest cells move, some proteins stopping their migration to that area and others encouraging the movement <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. After splitting apart, the first neural crest cells move ventrally and pass into the spaces between the somites and then, through the anterior portions of each segment until they arrive at the para-aortic sites, where they become the cells of the sympathetic ganglia and the adrenal medulla {{#pmid:19683477|PMID19683477}}. BMP-4 (bone morphogenetic protein 4) then acts on these neural crest cells, preventing them from becoming cells that have a neural function and causing them to become chromaffin cells at the adrenal medulla. Glucocorticoids then play a role in maintenance of chromaffin cells in postnatal life, this was only found recently, as previously it was thought that glucocorticoids were responsible entirely for the differentiation of neural crest cells into chromaffin, or adrenomedullary cells {{#pmid:23220335|PMID23220335}}.<br /> <br /> ===Anatomy and Functions===<br /> <br /> ----<br /> <br /> ====Anatomy and Histology====<br /> <br /> The adrenal medulla makes up the inner section of the adrenal glands, and is surrounded by the cortex, and a connective tissue capsule. It lies in the centre of the gland and it rarely measures no more than 2mm in thickness {{#pmid:21107679|PMID21107679}}. The cells of the adrenal medulla are derived from the neural crest as opposed to the mesodermal origins of the cortex. The adrenal medulla contains secretory cells called chromaffin cells due to the agents they produce when oxidised, such as chromate {{#pmid:11215683|PMID11215683}}. These cells secrete epinephrine, norepinephrine, chromogranin and neuropeptides in response to various substances such as acetylcholine <ref name="PMID11215683"/>. [[File:ADRENAL MEDULLA .jpg|600px|thumb|right|Adrenal Medulla Histology]]<br /> <br /> There are many types of highly differentiated cells in the adult adrenal medulla: <br /> - Epinephrine cells (90% of all chromaffin cells) {{#pmid:24715564|PMID24715564}}<br /> - Norepinephrine cells (10% of all chromaffin cells) <ref name="PMID24715564"/><br /> - Small granule-containing cells (SGCs) <ref name="PMID11215683"/><br /> <br /> These cells also synthesise, store and secrete catecholamines through controlled and regulated pathways <ref name="PMID24715564"/>, such as various peptides like substance P and neurotensin.These cells have unique neuroendocrine characteristics as a result of their neural-crest origin. They receive preganglionic innervation by thoracic splanchnic nerves, and could almost be considered a specialised sympathetic ganglion. With postganglgionic bodies, cells of the medulla are densely clustered around their vasculature for the secretion of hormones into the bloodstream to moderate the concentration of epinephrine and norepinephrine. The adrenal medulla also contains presynaptic sympathetic ganglion cells <ref name="PMID11215683"/>. The small granule-containing cells are usually found in clusters whereas, the ganglion cells are found either individually or in clusters, usually dispersed among the chromaffin cells or among the nerve fibres {{#pmid:18021328|PMID18021328}}. During embryonic development (around weeks 9-12), in contrast to the developing adrenal cortex, the medulla does not show evidence of an organised structure other than a small cluster of cells scattered throughout its cortex {{#pmid:30247985|PMID30247985}}. <br /> <br /> <br /> <br /> ====Related Anatomy====<br /> <br /> The tissue and organ structure of the adrenal medulla should be understood with regard to its specialised function within the sympathetic nervous system. <br /> <br /> The medullary region of the adrenal glands is tasked with the endocrine secretions of adrenaline and nor-adrenaline in response to environmental stressors that are signalled for by the sympathetic nervous system. That is, the secretion of fight-or-flight response hormones in order to restrict vasculature to the trunk and increase vascular activity in the peripheral musculature.<br /> <br /> The adrenal glands are supplied by several branches of the great vessels in the abdominal cavity. The secreted catecholamines in the medulla are directly able to pass to the blood stream this way.<br /> <br /> These adrenal glands and their contents are retroperitoneal in the adult and varied in shape, with the left often being semilunar and right being pyramidal. Nervous supply of the adrenal glands is achieved by contributions from the splanchnic nerves of the celiac plexus. {{#pmid:11215683|PMID11215683}} <br /> <br /> [[File:Dd.jpg|400px|thumb|right|Adult Adrenal Glands in situ]] <br /> ----<br /> ====Role of the Adrenal Medulla====<br /> <br /> Understanding the biochemistry of catecholamines is necessary to see how the adrenal medulla is designed in the stages of embryology and how it is suited for life in the neonate and adult. <br /> <br /> The epinephrine and norepinephrine in the neonate and adult work by primarily changing the osmoregulatory state of vasculature in organs. With the exclusion of their neuromodulatory and neurotransmitter functions, epinephrine and norepinephrine are mainly tasked with the control of sympathetic and parasympathetic supplies. <br /> <br /> Norepinephrine is a constrictor of peripheral vasculature by antagonising the action of surface receptors expressed on the endothelium of blood vessels, specifically Alpha-1 and Alpha-2 receptors, such that vascular resistance increases. <br /> <br /> Epinephrine is both a vasoconstrictor and vasodilator, depending on what receptors it attaches to. As a non-selective adrenergic agonist, it acts on Alpha-1, Alpha-2, Beta-1, Beta-2 and Beta-3 receptors that are found throughout the body's tissues, yielding many different physiological responses. {{#pmid:19396395|PMID19396395}}<br /> <br /> '''Adult Function'''<br /> <br /> While the adrenal cortex releases glucocorticoids in response to long term stress, the adrenal medulla releases its hormones in response to short-term, acute stress. The adrenal medulla contains the neuroendocrine chromaffin cells which are responsible for secreting adrenaline and noradrenaline. The function of these hormones is primarily to maintain the body’s homeostasis, especially of the internal organs, and to properly activate the autonomic stress response, more commonly known as the ‘fight or flight’ response {{#pmid:30237243|PMID30237243}}. Thus the function of the medulla includes signalling the liver and skeletal muscles to convert glycogen into glucose for increased energy. This results in increased blood glucose levels. These hormones also increase the heart rate, pulse and blood pressure in preparation for the fight or flight response. In addition to this, these hormones dilate the lung airways and prompt vasodilation to further increase oxygenation of important organs such as the lung, brain and heart. Vasoconstriction of blood vessels is also prompted to other less essential organs such as the bladder and the digestive system.<br /> <br /> Other effects also include pupil dilation, dry mouth and a loss in peripheral vision <ref name="PMID18021328"/>. Paramount to the correct response of chromaffin cells is the synaptic connection of the preganglionic cells which originate from the central nervous system and project axons into the adrenal medulla. While this is a very important relationship, the mechanisms of this remains unknown <ref name="PMID30237243"/>. In addition to the release of catecholamines, cells in the medulla also release peptides through the process of exocytosis from chromaffin granules, to help regulate blood pressure and regulation throughout the body. These peptides also regulate the release of adrenaline and noradrenaline, blood vessel contraction and the immune response <ref name="PMID18021328"/>. <br /> <br /> '''Embryonic function'''<br /> <br /> The current knowledge about the development of the adrenal gland is limited, with nearly all models being from animals, and very limited functional data available from human fetal adrenals <ref name="PMID30247985"/>. Thus for these reasons, there is scarce information available on the embryonic adrenal medullary functions. Nevertheless, there is accumulating evidence that the catecholamines in the fetal adrenal medulla plays an important role in the time of delivery by controlling thermogenesis and heart regulation {{#pmid:6998630|PMID6998630}}. <br /> <br /> The hormones released by the medulla during birth also play a key role for the newborn’s adaptation to extrauterine life. Despite the immaturity of the adrenal medulla at birth, it is known that respiratory, metabolic and cardiovascular changes during delivery are dependent on the adrenomedullary hormones {{#pmid:3280659|PMID3280659}}. Experimental data from human and animal fetal research shows that the fetal sympathoadrenal system, consisting of the adrenal medulla, sympathetic neurons and chromaffin tissue work together to maintain fetal homeostasis {{#pmid:6346884|PMID6346884}}. The adrenal medulla thus appears to provide vital physiological functions for fetal and neonatal survival, especially during birth. <br /> <br /> <br /> ----<br /> <br /> ===Molecular mechanisms/factors/genes===<br /> ----<br /> <br /> ====Genes and Transcription Factors Involved with the Adrenal Medulla's Development====<br /> <br /> The 'story' of the Adrenal Medulla's neural crest tissue begins at the process of neurulation, the formation of the neural tube from the folding neural plate, which is comprised of developing ectoderm which is opposite to the primitive streak. It is here that several key chemical players are at work. The classic interpretation of Sonic Hedgehog (Shh) and Wnt signalling pathways as the only mediators here, has been shown to be incorrect. Research has uncovered other signallers such as: <br /> <br /> *Bone-Morphogenic-Protein-4 (BMP4) for the regional expression of nervous system distinctions in the growing neural plate. This maintains two important embryonic trancription factors known as Paired-Box (PAX) Genes 3 and 7 which can allow for expression of neural crest markers HNK-1, SRY-Box (SOX) 8, 9 and 10 as the neural tube closes and the neural crest delaminates from the folding. {{#pmid:16688176|PMID16688176}} <br /> <br /> *Slug via Wnt signalling, this allows for the loosening of gap junctions in the extracellular matrix surrounding the newly-formed neural tube and trunk of the embryo. This extracellular matrix has chemo-attractant molecules<br /> <br /> [[File:Catecholamine_Synthesis.jpg|400px|thumb|right|Biochemical Cascade of Catecholamine Synthesis]]<br /> <br /> The importance of Somitogenesis and Neural Crest come to a head when neural crest cells must migrate anteriorly past somites 18 to 24 <br /> <br /> Members of the SOX gene family have multiple key contributors to Neural Crest in the Adrenal Medulla.<br /> <br /> <br /> Mouse models have demonstrated that SOX-10 knock-outs (mice whose DNA has been engineered to not express SOX-10) do not have an adrenal medulla. There has also been suggestion that SOX-8,9 and 10 are all strongly related to the migratory patterning of neural crest cells to the developing adrenal glands. {{#pmid:18272785|PMID18272785}}<br /> <br /> The TH gene (for Tyrosine Hydroxylase) encodes the aforementioned enzyme in the adrenal medulla and central nervous system. Tyrosine Hydroxylase is crucial in biochemical pathways and cascades for the synthesis of catecholamines and other CNS neurotransmitters. The conversion from L-Tyrosine to L-DOPA is dependent upon the catalytic action of Tyrosine Hydroxylase. From there, L-DOPA can make Dopamine and eventually Epinephrine and Norepinephrine as well. {{#pmid:19396395|PMID19396395}}<br /> <br /> ===Abnormalities/abnormal development===<br /> ----<br /> <br /> Abnormalities of the Adrenal Medulla are much less common than its mesoderm-derived shell of the Adrenal Gland. Three of the most notorious abnormalities of the Adrenal Medulla include:<br /> <br /> * Pheochromocytomas<br /> * Ganglioneuromas<br /> * Neuroblastomas<br /> <br /> <br /> Pheochromocytomas (PCCs) are variable neoplasias of the adrenal medulla's chromaffin cells. There are many classifications of PCCs, with autosomal-dominant germ-line mutations and heredities being one of the main causes. Familial phaeochromocytoma-paraganglioma (PGL) syndromes exist, with PGL1 having mutations of the SDHD gene, PGL3 being mutated of the SDHC gene and PGL4 having mutation of the SDHB gene. These phenotypically present as extra-adrenal chromaffin bodies, malformation of the adrenal glands themselves, absence of chromaffin bodies and fluctuations in circulating catecholamines. {{#pmid:18021328|PMID18021328}}<br /> <br /> Ganglioneuromas (GNs) are classically-benign growths that are very rare and arise from neural crest tissue. They are not circumscribed to the adrenal medulla, but also are found in the sympathetic chain and trunk ganglia. As a result of their scarcity, not much is known about them other than a few aberrant genes and generic clinical presentations. ERBB3, the receptor tyrosine kinas is understood to be important in the development of GNs, as well as an extremely high prevalence of up-regulated GATA3. A key thing to note is also the '''lack''' of N-MYC expression in GNs, which is quite prominent in neuroblastomas and other neoplasias. {{#pmid:29085827|PMID29085827}} {{#pmid:23715162|PMID23715162}} <br /> <br /> Neuroblastomas (NBs) are a more aggressive form of cancer, derived from neuroblasts - the precursor cells to neurons. A rather common pediatric cancer, they are often in children who are in risk factor groups such as those with aforementioned familial cancer syndromes, neurofibromatosis-1. These tumours often present with extremely variable catecholamine concentrations, which has implications for blood pressure, heart contractility and much more. Urinary excretion of norepinephrine, homovanillic acid (HVA) and vanilmandelic acid (VMA) can be used to help diagnose a suspected lesion of the adrenal gland, as these chemicals are associated with altered chemical cascades that are suspicious of neuroblastic change. {{#pmid:16372223|PMID16372223}}<br /> <br /> <br /> Apart from these abnormalities, there are other pathologies that may be connected to the adrenal medulla. One such example is a pathology of the Organ of Zuckerkandl. Also known as the para-aortic body, the Organ of Zuckerkandl is a primarily-gestational organ comprised of chromaffin cells and serves a similar purpose to the adrenal medulla in neonatal life.<br /> <br /> ===Animal models===<br /> ----<br /> Animal models are an integral part of research in embryology. In particular due to the moral concerns regarding the use of humans in scientific research. As a result different animals are used as substitutes to simulate the same environments and hope to achieve results that would also be able to represent humans as well. Prenatal adrenal gland development has been described in a number of scientific reports dating from the 1900s to studies in more recent years. These involved a variety of animal models such as ox, sheep, swine and most commonly mice. <br /> <br /> ====Chromaffin cells====<br /> There has been extensive research conducted into the adrenal chromaffin cells and their embryological developments. As explained above nueral crest cells are pluripotent meaning they are able to differentiate into multiple different cells{{#pmid:19377845|PMID19377845}}. The neural crest cells give rise to chromaffin cells of the adrenal medulla.<br /> <br /> =====Rat Models=====<br /> [[File:Adrenal gland.png|300px|thumb|right|3D images showing TH - positive cells accumulating at the cranial and audal ends of the adrenal gland. A. A observation of adrenal gland and surrounding structures (at 17 days of gestation). B. Enhanced image to further focus on the dark TH - positive cells. C. Image with the other structures removed.]]<br /> Previous research has reported that nueral crest cells differentiate into chromaffin cells around 19 days of gestation before forming the adrenal medulla{{#pmid:28684471|PMID2868441}}. Past research had also suggested that neural crest derived adrenal gland cells migrate using the sympathetic ganglia to the adrenal gland or preaortic ganglion, following different pathways, to reach their specific destination. However the results have shown that the pathways used to reach its destinations overlapped. This would suggest that there is a possibility of the cells using the same pathway to move from the beginning production to the destination that is the adrenal medulla (for chromaffin cells) and the preaortic ganglion (other cells involved in the sympathetic system). <br /> <br /> One particular study done by M.Yamato in 2004, along with his fellow scientists attempted to study the migration of neural crest cells in Wistar rats. In order to observe the formation adrenal medulla from the neural crest cells during the embryonic period, Yamato used anti - tyrosine hydroxylase (TH) antiserum injected into the rat embryos between 13-17 days of gestation. The anti - TH antiserum stain allows the scientists to visualize the neural crest cells under a light microscope. Later three dimensional images were created. From the images observed between 13 to 15 days of gestation, the TH - positive cells can be seen to move from the dorsal to the adrenal primordium{{#pmid:15240937|PMID15240937}}. After 16 days it was observed that a capsule had formed in some parts and TH - positive cells had penetrated the adrenal gland{{#pmid:15240937|PMID15240937}}. At seventeen days, TH - positive cells can be seen collecting at the medial part of the adrenal gland. The reconstructed images also shows that at the later stages during the 16-17 days of gestation, the accumulation of TH - positive cells grow and in combination with cell division leads to the formation of the adrenal medulla.<br /> <br /> =====Chicken models=====<br /> Chicken and rat models are often the most commonly used models when dealing with neural crest cells. In this particular review, collates multiple researchers results and presents evidence to discuss previous information suggesting that sympathetic neurons and chromaffin cells do not share a common progenitor{{#pmid:3693940|PMID3693940}}. The relevant study involved the use of cell cultures, Sympathoadrneal (SA) progenitor cells from embryonic(from chick embryos) and eary developmental stages were able to be procured. From these cultures it was easy to identify that glucocorticoids were crucial in the differentiation of SA cells into their derivatives, sympathetic neurons and chromaffin cells.<br /> <br /> [[File:Expression of BMP protein 4 .jpg|300px|thumb|right|Expression of BMP - 4 in the adrenal cortex at developmental stages. Shows the movement of the chromaffin progenitors moving from each stage of development. A-D: collection of progenitors outside E-H: cells have begun to penetrate the adrenal cortical region I-L: chromaffin cells have completely intergrated intergreted within the gland sg: sympathetic ganglia ac:adrenal cortical region ag: adrenal gland da: dorsal aortic region]]<br /> <br /> Another study conducted deals with the role of the bone morphogenetic protein(BMP-4) and its importance in the development of the adrenal medullary cells, chromaffin cells{{#pmid:18945349|PMID18945349}}. Previous research had shown that BMP - 4 a growth factor is plays an important role in the regulation of chromaffin cell production{{#pmid:10679774|PMID10679774}}. The researchers incubated chick embryos for 3 - 9 embryonic days and dissected them to be used for tissue cultures. Embryonic day 8 chick embryos had BMP - 4 overexpressing cells implanted in the sympathetic ganglia area, as well as other neurons which contained chromaffin like cells. What was observed was an increase in size and numbers of 'chromaffin' granules{{#pmid:18945349|PMID18945349}}. As a result it was concluded that although BMP - 4 promotes certain chromaffin traits, it does not have the capability to convert sympathetic neurons into a chromaffin type cell.<br /> <br /> ===Current research (labs)===<br /> ----<br /> <br /> ==== Generation of Adrenal Chromaffin-like Cells from Human Pluripotent Stem Cells====<br /> <br /> As explained above the adrenal medulla plays an important part in the autonomic system of an adult human. The chromaffin cells, in particular, are important neural crest derived cell that is closely related to the adrenal medulla. Previous findings have focused specifically on the mechanisms controlling the NCC migration and how these cells go on to form the different derivatives in their particular destinations in the embryo. For example, as previously explained studies have shown that chromaffin cells have been observed to move to the adrenal gland to form the medulla of the adrenal gland. This report goes through a recent study that involves the adrenal medullary cells, in particular chromaffin cells, and their potential to be used to model certain pathological diseases related to these cells. This is part of a study that also involves neural crest cells and their ability to differentiate into multiple different types of cells<ref>Lumb, R., & Schwarz, Q. (2015). Sympathoadrenal neural crest cells: The known, unknown and forgotten?. Development, Growth & Differentiation, 57(2), 146-157. doi: 10.1111/dgd.12189</ref>. Neural crest cells and SAPs from human embryonic cells and induced pluripotent stem cells were generated to be used in the experiment. By exposing the pluripotent stem cells to BMP4 in vitro, results showed that these cells would 'upregulate' the chromaffin cell - specific marker PMNT (an enzyme that synthesizes adrenaline). Furthermore when the cells from human embryos were implanted into avian embryos, there was a visible potential for the human cells to differentiate into cells that expressed the chromaffin cell markers{{#pmid:5768882|PMID5768882}}.<br /> <br /> <br /> ====Multipotent Peripheral Glial Cells Generate Neuroendocrine Cells of the Adrenal Medulla====<br /> <br /> Similar to the first study, this one also focuses on the chromaffin cells and their relationship to the adrenal medulla. Chromaffin cells often represent the main endocrine component that is believed to differentiate from neural crest cells{{#pmid:28684471|PMID28684471}}. The study focuses specifically on the idea that previous research has suggested that nerve - associated schwann cell precursor is a progenitor of chromaffin cells. What the findings suggested was that peripheral nerves provided migration routes for the progenitors. This is backed up by the results, a high concentration of chromaffin cells can be found being derived from the nerve, as nerve ablated mice in the experiment showed a large difference of 78% less cells compared to the control. Other than this, the study also brought to light the proliferative potential of the cells from nerves, with different other cell types being discovered as well (including cells such as parasympathetic{{#pmid:24925912|PMID24925912}} and melanocytes {{#pmid:19837037 |PMID19837037}}). The findings would provide useful information into further understanding the adrenal gland and its embryonic origins (as there is still much to learn regarding the formation of the adrenal medulla) but also pathological diseases such as neuroblastoma and pheochromatocytoma which are most common in the adrenal glandular region {{#pmid:23106811|PMID23106811}}.<br /> <br /> ===Glossary===<br /> ----<br /> ===Reference list===</div>

Z5091101 https://embryology.med.unsw.edu.au/embryology/index.php?title=2018_Group_Project_1&diff=358297 2018 Group Project 1 2018-10-16T00:39:24Z

<p>Z5091101: /* Introduction */</p> <hr /> <div>=The Contribution of Neural Crest Cells to the Adrenal Medulla=<br /> ----<br /> {{2018ANAT2341ProjectHeader}}<br /> <br /> <br /> ===Introduction===<br /> <br /> ----<br /> <br /> The neural crest of an embryo migrates and differentiates to form various components of the body. This transient population of pluripotent stem-cells give rise to many complex and different structures across the adult by chemical signalling. One of these tissues is the medulla of the adrenal gland which is involved in the production of epinephrine and norepinephrine. This project will comprehensively outline the history of neural crest research, the embryonic developmental time course, tissue and organ structure, molecular mechanisms, abnormalities, animal models and current research.<br /> <br /> ===History===<br /> ----<br /> '''Describing the neural crest'''<br /> [[File:Wilhelm_His_History_Wilhelm.jpeg|left|230px|thumb|Wilhelm His]]<br /> The "neural crest" is a structure in the embryo and is the junction between the neural and epidermal ectoderm. It is exclusive to vertebrates and forms a range of structures{{#pmid:22230617|PMID22230617}}. The neural crest contributes a large number of cells of varying structure and function that directly or indirectly contribute to the development of tissues and organs within the body {{#pmid:19179766|PMID19179766}}. In 1868, the neural crest cells were first identified in a chick embryo as a collection of cells known as "Zwischenstrang" by Professor Wilhelm His {{#pmid:22820859|PMID22820859}}. Wilhelm His was among the first to provide an explanation for the mechanics governing the developing embryo as well as the physiology and the organs that the differing germinal regions would eventually give rise to. In 1878, the term neural ridge was used to describe this collection of cells but the term neural crest was later coined by Arthur Milnes Marshall in 1879 in a paper he worked on disseminating the knowledge from his research on the development of cranial nerves in chicken embryos. {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1890s-1950s'''<br /> The neural crest is the point of origin for spinal/cranial ganglia and neurons. This theory received little criticism and was not contested much by other researchers prior to the 1890s. This is owing to the fact that the neural crest is quite closely related to the neural tube and thus this relationship makes sense. This discovery was made by His and Marshall, however, they found this out independently of one another.In the 1890s, Julia Platt, claimed that odontoblasts as well as the cartilages forming the facial and pharyngeal arch skeletons came from the ectoderm. This created much debate and was contested by many{{#pmid:22820859|PMID22820859}}. <br /> <br /> This is because this theory completely contradicted the germ-layer theory, whereby skeletal tissues originate at the mesoderm and not the ectoderm. The controversies this finding created brought about a slowing down of research, as demonstrated by a gap of almost 40 years between the theory that skeletal tissues originating from the neural crest. Today, it is known that the neural crest does indeed play a role in the development of the skeleton in vertebrates, particularly, the cranial neural crest. Although these studies were occurring, the focus was still primarily on researching pigment cells and ganglia of the spine up until the 1950s, when Sven Hörstadius' major work on the neural crest was published, titled "The Neural Crest: Its properties and derivatives in the light of experimental research". This work focused on experimental data tracing the development of the cartilaginous skeleton derived from the neural crest {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1960s - 1970s'''<br /> In the 1960s, the migration patterns of neural crest cells were studied in avian embryos (birds). This was a shift from studying the embryos of amphibians. This was inspired by studies conducted in the 1960s on neural crest cells migrating from the brain and spinal cord, known as trunk and cranial neural crest cells {{#pmid:19179766|PMID19179766}}. The cranial neural crest eventually becomes the bones, cartilage and connective tissues forming the foundation of the face, ears and teeth. The trunk neural crest cells can either become melanocytes or can migrate into sclerotomes which are later contributors to the cartilage of the spine and the dorsal root ganglia {{#pmid:22820859|PMID22820859}}. The cells in the trunk neural crest that migrate vertically become the sympathetic ganglia, the nerves proximal to the aorta and the adrenal medulla <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. In the 1970s many detailed maps signifying the pathways of many of the neural crest cells appeared as well as an understanding that the environment in which the neural crest cells are found plays a major role in their final development as well as the occurrences of abnormalities in the fetus {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1980s - 21st century'''<br /> [[File:Regions_of_NC_Cells.jpg|left|Neural crest regions|thumb|500px]]<br /> From the 1980s-1990s, the causative agent of organ transformation from one to another (homeotic patterning), as well as the Hox genes which regulate the axis of most symmetrical animal embryos were founded and studied. The neural crest, which previously was divided into the cranial and trunk regions, was now further divided into the vagal and sacral neural crest, the cardiac neural crest and the cephalic neural crest {{#pmid:19179766|PMID19179766}}. The vagal & sacral neural crest gives rise to the parasympathetic ganglia found in the gut. Without these ganglia, peristalsis, is not possible <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. The cardiac neural crest contributes to the valves, septa and major blood vessels of the heart, as well as connective tissues and cartilage{{#pmid:19179766|PMID19179766}}. This is important for the structure of the heart as well as its overall function, enabling it to move blood around the body efficiently as well as keep pulmonary and aortic circulation separated <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> <br /> <br /> Today, knowledge of the neural crest cells, their migration patterns, modes of differentiation, derivatives and apoptosis (cell death) are being studied extensively. This is being done on a comparative basis between different organisms, to add further evidence for evolution {{#pmid:19179766|PMID19179766}}. The neural crest is definitely forging a "crest" between the fields of developmental and evolutionary biology, as it is a structure '''shared exclusively by all vertebrates'''. Invertebrates do not derive their specialised cells from the neural crest as they do not have one, rather, they derive these from the endomesoderm {{#pmid:22230617|PMID22230617}}.<br /> <br /> '''Future directions'''<br /> <br /> Since its discovery by His, the neural crest field has made great progress, from studies performed on the structure, to analysis of the molecules and whether certain aspects of the neural crest are specific to a single species of organism, or to all vertebrates collectively. Future work on the cranial neural crest needs to be done as well as identifying and categorising the networks responsible for the proliferation and death of cells, as well as how the cells move and migrate, as well as the gene regulatory networks (GRNs) that regulate the synthesis of proteins. Advances in technology will undeniably lead us to more answers on the subject {{#pmid:22230617|PMID22230617}}.<br /> <br /> ===Developmental time course===<br /> ---- <br /> <br /> [[File:Adrenal_Medulla_Developmental_Timeline.jpg|right|thumb|500px]]<br /> <br /> The adrenal gland has two distinct sections, the cortex and the medulla, both with different embryonic origins. The cortex accounts for 90% of the adrenal glands and arises from intermediate mesoderm. The medulla only accounts for 10% of the adult adrenal glands, however it has neural crest embryonic origin. The medulla consists of chromaffinoblast cells which are migrant neuroblast cells from the neural crest, therefore the adrenal medulla is a component of the sympathetic nervous system.{{#pmid:21175739|PMID21175739}} Neural crest cells replicate in week 7 and begin to differentiate in week 8, the cells then migrate to the developing adrenal gland in week 9 of development.{{#pmid:25255746|PMID25255746}}{{#pmid:18279781|PMID18279781}} The neural crest cells infiltrate the cortex and the chromaffin cells are scattered islands in the cortex.{{#pmid:23354096|PMID23354096}} Throughout development the cells will become more compact in the centre of the gland, during this period of development the adrenal gland is growing rapidly. The gland is abnormally large until the second trimester and the medulla is much thicker prenatally.{{#pmid:18279781|PMID18279781}}{{#pmid:21175739|PMID21175739}}<br /> <br /> <br /> ===Embryonic origins===<br /> ----<br /> [[File:Trunk_NCC_migration.jpg|left|450px|thumb|Trunk NCC migration]]<br /> The adrenal gland is made up of the adrenal cortex and adrenal medulla, which both have different embryonic origins. The adrenal medulla arises from the neural crest tissue, found near the level of the coeliac plexus & sympathetic ganglion at somites 18-24 {{#pmid:16124976|PMID16124976}}. Specifically, this neural crest tissue comes from the trunk neural crest cells (see above figure to determine the approximate location in an embryo) <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> The trunk neural crest coordinates the development of the endocrine system, secretory cells, the peripheral nervous system and, to some degree, skeletal development, as well as innervation of the intestine {{#pmid: 28287247|PMID 28287247}}. The trunk neural cells arise caudally, undergo an epithelial to mesenchymal transition and follow three migratory pathways {{#pmid:20399766|PMID20399766}}.<br /> [[File:Differentiation_of_NCC.jpg|left|580px|thumb|Differentiation of chromaffin cells]]<br /> - A dorsolateral pathway (between ectoderm and somites), these become melanocytes, travel up to the point of the dermis and become a major part of the hair follicles and skin <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> - A ventrolateral pathway (through the somites)<br /> - A ventromedial pathway (between neural tube and posterior schlerotome){{#pmid:20399766|PMID20399766}}.<br /> <br /> Migration of neural crest cells from the sympathetic ganglion is what leads to the development of the adrenal medulla. In week 8 of development, immature cells called neuroblasts migrate through to the inner portion of the medulla, where they become the adrenal medulla {{#pmid:19683477|PMID19683477}}. Chromaffin cells are neuroendocrine cells and are found in the sympathetic ganglia and make up the majority of the adrenal medulla{{#pmid:19683477|PMID19683477}}. They synthesise and release a range of hormones in the body and arise from the temporary neural crest. The term chromaffin was inspired by the staining capacity of these cells when they came into contact with chrome salts. They make, store, export and use catecholamines, responsible for making noradrenaline and originate at the caudal region of somites 18-24 of the neural crest, also known as the adrenomedullary region {{#pmid:19683477|PMID19683477}}.<br /> <br /> For cells to leave the neural crest and begin their migration, certain conditions need to be met, that is, the cells need to be loosely connected, their tight junctions becoming relaxed, initiated by "Slug protein" and a loss of N-Cadherin which also leads to the loosening of these junctions. The surrounding matrix as well as chemotactic and stem cell factors of the neural tube are then what dictates how the neural crest cells move, some proteins stopping their migration to that area and others encouraging the movement <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. After splitting apart, the first neural crest cells move ventrally and pass into the spaces between the somites and then, through the anterior portions of each segment until they arrive at the para-aortic sites, where they become the cells of the sympathetic ganglia and the adrenal medulla {{#pmid:19683477|PMID19683477}}. BMP-4 (bone morphogenetic protein 4) then acts on these neural crest cells, preventing them from becoming cells that have a neural function and causing them to become chromaffin cells at the adrenal medulla. Glucocorticoids then play a role in maintenance of chromaffin cells in postnatal life, this was only found recently, as previously it was thought that glucocorticoids were responsible entirely for the differentiation of neural crest cells into chromaffin, or adrenomedullary cells {{#pmid:23220335|PMID23220335}}.<br /> <br /> ===Anatomy and Functions===<br /> <br /> ----<br /> <br /> ====Anatomy and Histology====<br /> <br /> The adrenal medulla makes up the inner section of the adrenal glands, and is surrounded by the cortex, and a connective tissue capsule. It lies in the centre of the gland and it rarely measures no more than 2mm in thickness {{#pmid:21107679|PMID21107679}}. The cells of the adrenal medulla are derived from the neural crest as opposed to the mesodermal origins of the cortex. The adrenal medulla contains secretory cells called chromaffin cells due to the agents they produce when oxidised, such as chromate {{#pmid:11215683|PMID11215683}}. These cells secrete epinephrine, norepinephrine, chromogranin and neuropeptides in response to various substances such as acetylcholine <ref name="PMID11215683"/>. [[File:ADRENAL MEDULLA .jpg|600px|thumb|right|Adrenal Medulla Histology]]<br /> <br /> There are many types of highly differentiated cells in the adult adrenal medulla: <br /> - Epinephrine cells (90% of all chromaffin cells) {{#pmid:24715564|PMID24715564}}<br /> - Norepinephrine cells (10% of all chromaffin cells) <ref name="PMID24715564"/><br /> - Small granule-containing cells (SGCs) <ref name="PMID11215683"/><br /> <br /> These cells also synthesise, store and secrete catecholamines through controlled and regulated pathways <ref name="PMID24715564"/>, such as various peptides like substance P and neurotensin.These cells have unique neuroendocrine characteristics as a result of their neural-crest origin. They receive preganglionic innervation by thoracic splanchnic nerves, and could almost be considered a specialised sympathetic ganglion. With postganglgionic bodies, cells of the medulla are densely clustered around their vasculature for the secretion of hormones into the bloodstream to moderate the concentration of epinephrine and norepinephrine. The adrenal medulla also contains presynaptic sympathetic ganglion cells <ref name="PMID11215683"/>. The small granule-containing cells are usually found in clusters whereas, the ganglion cells are found either individually or in clusters, usually dispersed among the chromaffin cells or among the nerve fibres {{#pmid:18021328|PMID18021328}}. During embryonic development (around weeks 9-12), in contrast to the developing adrenal cortex, the medulla does not show evidence of an organised structure other than a small cluster of cells scattered throughout its cortex {{#pmid:30247985|PMID30247985}}. <br /> <br /> <br /> <br /> ====Related Anatomy====<br /> <br /> The tissue and organ structure of the adrenal medulla should be understood with regard to its specialised function within the sympathetic nervous system. <br /> <br /> The medullary region of the adrenal glands is tasked with the endocrine secretions of adrenaline and nor-adrenaline in response to environmental stressors that are signalled for by the sympathetic nervous system. That is, the secretion of fight-or-flight response hormones in order to restrict vasculature to the trunk and increase vascular activity in the peripheral musculature.<br /> <br /> The adrenal glands are supplied by several branches of the great vessels in the abdominal cavity. The secreted catecholamines in the medulla are directly able to pass to the blood stream this way.<br /> <br /> These adrenal glands and their contents are retroperitoneal in the adult and varied in shape, with the left often being semilunar and right being pyramidal. Nervous supply of the adrenal glands is achieved by contributions from the splanchnic nerves of the celiac plexus. {{#pmid:11215683|PMID11215683}} <br /> <br /> [[File:Dd.jpg|400px|thumb|right|Adult Adrenal Glands in situ]] <br /> ----<br /> ====Role of the Adrenal Medulla====<br /> <br /> Understanding the biochemistry of catecholamines is necessary to see how the adrenal medulla is designed in the stages of embryology and how it is suited for life in the neonate and adult. <br /> <br /> The epinephrine and norepinephrine in the neonate and adult work by primarily changing the osmoregulatory state of vasculature in organs. With the exclusion of their neuromodulatory and neurotransmitter functions, epinephrine and norepinephrine are mainly tasked with the control of sympathetic and parasympathetic supplies. <br /> <br /> Norepinephrine is a constrictor of peripheral vasculature by antagonising the action of surface receptors expressed on the endothelium of blood vessels, specifically Alpha-1 and Alpha-2 receptors, such that vascular resistance increases. <br /> <br /> Epinephrine is both a vasoconstrictor and vasodilator, depending on what receptors it attaches to. As a non-selective adrenergic agonist, it acts on Alpha-1, Alpha-2, Beta-1, Beta-2 and Beta-3 receptors that are found throughout the body's tissues, yielding many different physiological responses. {{#pmid:19396395|PMID19396395}}<br /> <br /> '''Adult Function'''<br /> <br /> While the adrenal cortex releases glucocorticoids in response to long term stress, the adrenal medulla releases its hormones in response to short-term, acute stress. The adrenal medulla contains the neuroendocrine chromaffin cells which are responsible for secreting adrenaline and noradrenaline. The function of these hormones is primarily to maintain the body’s homeostasis, especially of the internal organs, and to properly activate the autonomic stress response, more commonly known as the ‘fight or flight’ response {{#pmid:30237243|PMID30237243}}. Thus the function of the medulla includes signalling the liver and skeletal muscles to convert glycogen into glucose for increased energy. This results in increased blood glucose levels. These hormones also increase the heart rate, pulse and blood pressure in preparation for the fight or flight response. In addition to this, these hormones dilate the lung airways and prompt vasodilation to further increase oxygenation of important organs such as the lung, brain and heart. Vasoconstriction of blood vessels is also prompted to other less essential organs such as the bladder and the digestive system.<br /> <br /> Other effects also include pupil dilation, dry mouth and a loss in peripheral vision <ref name="PMID18021328"/>. Paramount to the correct response of chromaffin cells is the synaptic connection of the preganglionic cells which originate from the central nervous system and project axons into the adrenal medulla. While this is a very important relationship, the mechanisms of this remains unknown <ref name="PMID30237243"/>. In addition to the release of catecholamines, cells in the medulla also release peptides through the process of exocytosis from chromaffin granules, to help regulate blood pressure and regulation throughout the body. These peptides also regulate the release of adrenaline and noradrenaline, blood vessel contraction and the immune response <ref name="PMID18021328"/>. <br /> <br /> '''Embryonic function'''<br /> <br /> The current knowledge about the development of the adrenal gland is limited, with nearly all models being from animals, and very limited functional data available from human fetal adrenals <ref name="PMID30247985"/>. Thus for these reasons, there is scarce information available on the embryonic adrenal medullary functions. Nevertheless, there is accumulating evidence that the catecholamines in the fetal adrenal medulla plays an important role in the time of delivery by controlling thermogenesis and heart regulation {{#pmid:6998630|PMID6998630}}. <br /> <br /> The hormones released by the medulla during birth also play a key role for the newborn’s adaptation to extrauterine life. Despite the immaturity of the adrenal medulla at birth, it is known that respiratory, metabolic and cardiovascular changes during delivery are dependent on the adrenomedullary hormones {{#pmid:3280659|PMID3280659}}. Experimental data from human and animal fetal research shows that the fetal sympathoadrenal system, consisting of the adrenal medulla, sympathetic neurons and chromaffin tissue work together to maintain fetal homeostasis {{#pmid:6346884|PMID6346884}}. The adrenal medulla thus appears to provide vital physiological functions for fetal and neonatal survival, especially during birth. <br /> <br /> <br /> ----<br /> <br /> ===Molecular mechanisms/factors/genes===<br /> ----<br /> <br /> ====Genes and Transcription Factors Involved with the Adrenal Medulla's Development====<br /> <br /> The 'story' of the Adrenal Medulla's neural crest tissue begins at the process of neurulation, the formation of the neural tube from the folding neural plate, which is comprised of developing ectoderm which is opposite to the primitive streak. It is here that several key chemical players are at work. The classic interpretation of Sonic Hedgehog (Shh) and Wnt signalling pathways as the only mediators here, has been shown to be incorrect. Research has uncovered other signallers such as: <br /> <br /> *Bone-Morphogenic-Protein-4 (BMP4) for the regional expression of nervous system distinctions in the growing neural plate. This maintains two important embryonic trancription factors known as Paired-Box (PAX) Genes 3 and 7 which can allow for expression of neural crest markers HNK-1, SRY-Box (SOX) 8, 9 and 10 as the neural tube closes and the neural crest delaminates from the folding. {{#pmid:16688176|PMID16688176}} <br /> <br /> *Slug via Wnt signalling, this allows for the loosening of gap junctions in the extracellular matrix surrounding the newly-formed neural tube and trunk of the embryo. This extracellular matrix has chemo-attractant molecules<br /> <br /> [[File:Catecholamine_Synthesis.jpg|400px|thumb|right|Biochemical Cascade of Catecholamine Synthesis]]<br /> <br /> The importance of Somitogenesis and Neural Crest come to a head when neural crest cells must migrate anteriorly past somites 18 to 24 <br /> <br /> Members of the SOX gene family have multiple key contributors to Neural Crest in the Adrenal Medulla.<br /> <br /> <br /> Mouse models have demonstrated that SOX-10 knock-outs (mice whose DNA has been engineered to not express SOX-10) do not have an adrenal medulla. There has also been suggestion that SOX-8,9 and 10 are all strongly related to the migratory patterning of neural crest cells to the developing adrenal glands. {{#pmid:18272785|PMID18272785}}<br /> <br /> The TH gene (for Tyrosine Hydroxylase) encodes the aforementioned enzyme in the adrenal medulla and central nervous system. Tyrosine Hydroxylase is crucial in biochemical pathways and cascades for the synthesis of catecholamines and other CNS neurotransmitters. The conversion from L-Tyrosine to L-DOPA is dependent upon the catalytic action of Tyrosine Hydroxylase. From there, L-DOPA can make Dopamine and eventually Epinephrine and Norepinephrine as well. {{#pmid:19396395|PMID19396395}}<br /> <br /> ===Abnormalities/abnormal development===<br /> ----<br /> <br /> Abnormalities of the Adrenal Medulla are much less common than its mesoderm-derived shell of the Adrenal Gland. Three of the most notorious abnormalities of the Adrenal Medulla include:<br /> <br /> * Pheochromocytomas<br /> * Ganglioneuromas<br /> * Neuroblastomas<br /> <br /> <br /> Pheochromocytomas (PCCs) are variable neoplasias of the adrenal medulla's chromaffin cells. There are many classifications of PCCs, with autosomal-dominant germ-line mutations and heredities being one of the main causes. Familial phaeochromocytoma-paraganglioma (PGL) syndromes exist, with PGL1 having mutations of the SDHD gene, PGL3 being mutated of the SDHC gene and PGL4 having mutation of the SDHB gene. These phenotypically present as extra-adrenal chromaffin bodies, malformation of the adrenal glands themselves, absence of chromaffin bodies and fluctuations in circulating catecholamines. {{#pmid:18021328|PMID18021328}}<br /> <br /> Ganglioneuromas (GNs) are classically-benign growths that are very rare and arise from neural crest tissue. They are not circumscribed to the adrenal medulla, but also are found in the sympathetic chain and trunk ganglia. As a result of their scarcity, not much is known about them other than a few aberrant genes and generic clinical presentations. ERBB3, the receptor tyrosine kinas is understood to be important in the development of GNs, as well as an extremely high prevalence of up-regulated GATA3. A key thing to note is also the '''lack''' of N-MYC expression in GNs, which is quite prominent in neuroblastomas and other neoplasias. {{#pmid:29085827|PMID29085827}} {{#pmid:23715162|PMID23715162}} <br /> <br /> Neuroblastomas (NBs) are a more aggressive form of cancer, derived from neuroblasts - the precursor cells to neurons. A rather common pediatric cancer, they are often in children who are in risk factor groups such as those with aforementioned familial cancer syndromes, neurofibromatosis-1. These tumours often present with extremely variable catecholamine concentrations, which has implications for blood pressure, heart contractility and much more. Urinary excretion of norepinephrine, homovanillic acid (HVA) and vanilmandelic acid (VMA) can be used to help diagnose a suspected lesion of the adrenal gland, as these chemicals are associated with altered chemical cascades that are suspicious of neuroblastic change. {{#pmid:16372223|PMID16372223}}<br /> <br /> <br /> Apart from these abnormalities, there are other pathologies that may be connected to the adrenal medulla. One such example is a pathology of the Organ of Zuckerkandl. Also known as the para-aortic body, the Organ of Zuckerkandl is a primarily-gestational organ comprised of chromaffin cells and serves a similar purpose to the adrenal medulla in neonatal life.<br /> <br /> ===Animal models===<br /> ----<br /> Animal models are an integral part of research in embryology. In particular due to the moral concerns regarding the use of humans in scientific research. As a result different animals are used as substitutes to simulate the same environments and hope to achieve results that would also be able to represent humans as well. Prenatal adrenal gland development has been described in a number of scientific reports dating from the 1900s to studies in more recent years. These involved a variety of animal models such as ox, sheep, swine and most commonly mice. <br /> <br /> ====Chromaffin cells====<br /> There has been extensive research conducted into the adrenal chromaffin cells and their embryological developments. As explained above nueral crest cells are pluripotent meaning they are able to differentiate into multiple different cells{{#pmid:19377845|PMID19377845}}. The neural crest cells give rise to chromaffin cells of the adrenal medulla.<br /> <br /> =====Rat Models=====<br /> [[File:Adrenal gland.png|300px|thumb|right|3D images showing TH - positive cells accumulating at the cranial and audal ends of the adrenal gland. A. A observation of adrenal gland and surrounding structures (at 17 days of gestation). B. Enhanced image to further focus on the dark TH - positive cells. C. Image with the other structures removed.]]<br /> Previous research has reported that nueral crest cells differentiate into chromaffin cells around 19 days of gestation before forming the adrenal medulla{{#pmid:28684471|PMID2868441}}. Past research had also suggested that neural crest derived adrenal gland cells migrate using the sympathetic ganglia to the adrenal gland or preaortic ganglion, following different pathways, to reach their specific destination. However the results have shown that the pathways used to reach its destinations overlapped. This would suggest that there is a possibility of the cells using the same pathway to move from the beginning production to the destination that is the adrenal medulla (for chromaffin cells) and the preaortic ganglion (other cells involved in the sympathetic system). <br /> <br /> One particular study done by M.Yamato in 2004, along with his fellow scientists attempted to study the migration of neural crest cells in Wistar rats. In order to observe the formation adrenal medulla from the neural crest cells during the embryonic period, Yamato used anti - tyrosine hydroxylase (TH) antiserum injected into the rat embryos between 13-17 days of gestation. The anti - TH antiserum stain allows the scientists to visualize the neural crest cells under a light microscope. Later three dimensional images were created. From the images observed between 13 to 15 days of gestation, the TH - positive cells can be seen to move from the dorsal to the adrenal primordium{{#pmid:15240937|PMID15240937}}. After 16 days it was observed that a capsule had formed in some parts and TH - positive cells had penetrated the adrenal gland{{#pmid:15240937|PMID15240937}}. At seventeen days, TH - positive cells can be seen collecting at the medial part of the adrenal gland. The reconstructed images also shows that at the later stages during the 16-17 days of gestation, the accumulation of TH - positive cells grow and in combination with cell division leads to the formation of the adrenal medulla.<br /> <br /> =====Chicken models=====<br /> Chicken and rat models are often the most commonly used models when dealing with neural crest cells. In this particular review, collates multiple researchers results and presents evidence to discuss previous information suggesting that sympathetic neurons and chromaffin cells do not share a common progenitor{{#pmid:3693940|PMID3693940}}. The relevant study involved the use of cell cultures, Sympathoadrneal (SA) progenitor cells from embryonic(from chick embryos) and eary developmental stages were able to be procured. From these cultures it was easy to identify that glucocorticoids were crucial in the differentiation of SA cells into their derivatives, sympathetic neurons and chromaffin cells.<br /> <br /> [[File:Expression of BMP protein 4 .jpg|300px|thumb|right|Expression of BMP - 4 in the adrenal cortex at developmental stages. Shows the movement of the chromaffin progenitors moving from each stage of development. A-D: collection of progenitors outside E-H: cells have begun to penetrate the adrenal cortical region I-L: chromaffin cells have completely intergrated intergreted within the gland sg: sympathetic ganglia ac:adrenal cortical region ag: adrenal gland da: dorsal aortic region]]<br /> <br /> Another study conducted deals with the role of the bone morphogenetic protein(BMP-4) and its importance in the development of the adrenal medullary cells, chromaffin cells{{#pmid:18945349|PMID18945349}}. Previous research had shown that BMP - 4 a growth factor is plays an important role in the regulation of chromaffin cell production{{#pmid:10679774|PMID10679774}}. The researchers incubated chick embryos for 3 - 9 embryonic days and dissected them to be used for tissue cultures. Embryonic day 8 chick embryos had BMP - 4 overexpressing cells implanted in the sympathetic ganglia area, as well as other neurons which contained chromaffin like cells. What was observed was an increase in size and numbers of 'chromaffin' granules{{#pmid:18945349|PMID18945349}}. As a result it was concluded that although BMP - 4 promotes certain chromaffin traits, it does not have the capability to convert sympathetic neurons into a chromaffin type cell.<br /> <br /> ===Current research (labs)===<br /> ----<br /> <br /> ==== Generation of Adrenal Chromaffin-like Cells from Human Pluripotent Stem Cells====<br /> <br /> As explained above the adrenal medulla plays an important part in the autonomic system of an adult human. The chromaffin cells, in particular, are important neural crest derived cell that is closely related to the adrenal medulla. Previous findings have focused specifically on the mechanisms controlling the NCC migration and how these cells go on to form the different derivatives in their particular destinations in the embryo. For example, as previously explained studies have shown that chromaffin cells have been observed to move to the adrenal gland to form the medulla of the adrenal gland. This report goes through a recent study that involves the adrenal medullary cells, in particular chromaffin cells, and their potential to be used to model certain pathological diseases related to these cells. This is part of a study that also involves neural crest cells and their ability to differentiate into multiple different types of cells<ref>Lumb, R., & Schwarz, Q. (2015). Sympathoadrenal neural crest cells: The known, unknown and forgotten?. Development, Growth & Differentiation, 57(2), 146-157. doi: 10.1111/dgd.12189</ref>. Neural crest cells and SAPs from human embryonic cells and induced pluripotent stem cells were generated to be used in the experiment. By exposing the pluripotent stem cells to BMP4 in vitro, results showed that these cells would 'upregulate' the chromaffin cell - specific marker PMNT (an enzyme that synthesizes adrenaline). Furthermore when the cells from human embryos were implanted into avian embryos, there was a visible potential for the human cells to differentiate into cells that expressed the chromaffin cell markers{{#pmid:5768882|PMID5768882}}.<br /> <br /> <br /> ====Multipotent Peripheral Glial Cells Generate Neuroendocrine Cells of the Adrenal Medulla====<br /> <br /> Similar to the first study, this one also focuses on the chromaffin cells and their relationship to the adrenal medulla. Chromaffin cells often represent the main endocrine component that is believed to differentiate from neural crest cells{{#pmid:28684471|PMID28684471}}. The study focuses specifically on the idea that previous research has suggested that nerve - associated schwann cell precursor is a progenitor of chromaffin cells. What the findings suggested was that peripheral nerves provided migration routes for the progenitors. This is backed up by the results, a high concentration of chromaffin cells can be found being derived from the nerve, as nerve ablated mice in the experiment showed a large difference of 78% less cells compared to the control. Other than this, the study also brought to light the proliferative potential of the cells from nerves, with different other cell types being discovered as well (including cells such as parasympathetic{{#pmid:24925912|PMID24925912}} and melanocytes {{#pmid:19837037 |PMID19837037}}). The findings would provide useful information into further understanding the adrenal gland and its embryonic origins (as there is still much to learn regarding the formation of the adrenal medulla) but also pathological diseases such as neuroblastoma and pheochromatocytoma which are most common in the adrenal glandular region {{#pmid:23106811|PMID23106811}}.<br /> <br /> ===Glossary===<br /> ----<br /> ===Reference list===</div>

Z5091101 https://embryology.med.unsw.edu.au/embryology/index.php?title=2018_Group_Project_1&diff=358295 2018 Group Project 1 2018-10-16T00:39:04Z

<p>Z5091101: /* Introduction */</p> <hr /> <div>=The Contribution of Neural Crest Cells to the Adrenal Medulla=<br /> ----<br /> {{2018ANAT2341ProjectHeader}}<br /> <br /> <br /> ===Introduction===<br /> <br /> ----<br /> [[File:NC Location.jpg|right|450px|thumb|The neural crest]]<br /> <br /> The neural crest of an embryo migrates and differentiates to form various components of the body. This transient population of pluripotent stem-cells give rise to many complex and different structures across the adult by chemical signalling. One of these tissues is the medulla of the adrenal gland which is involved in the production of epinephrine and norepinephrine. This project will comprehensively outline the history of neural crest research, the embryonic developmental time course, tissue and organ structure, molecular mechanisms, abnormalities, animal models and current research.<br /> <br /> ===History===<br /> ----<br /> '''Describing the neural crest'''<br /> [[File:Wilhelm_His_History_Wilhelm.jpeg|left|230px|thumb|Wilhelm His]]<br /> The "neural crest" is a structure in the embryo and is the junction between the neural and epidermal ectoderm. It is exclusive to vertebrates and forms a range of structures{{#pmid:22230617|PMID22230617}}. The neural crest contributes a large number of cells of varying structure and function that directly or indirectly contribute to the development of tissues and organs within the body {{#pmid:19179766|PMID19179766}}. In 1868, the neural crest cells were first identified in a chick embryo as a collection of cells known as "Zwischenstrang" by Professor Wilhelm His {{#pmid:22820859|PMID22820859}}. Wilhelm His was among the first to provide an explanation for the mechanics governing the developing embryo as well as the physiology and the organs that the differing germinal regions would eventually give rise to. In 1878, the term neural ridge was used to describe this collection of cells but the term neural crest was later coined by Arthur Milnes Marshall in 1879 in a paper he worked on disseminating the knowledge from his research on the development of cranial nerves in chicken embryos. {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1890s-1950s'''<br /> The neural crest is the point of origin for spinal/cranial ganglia and neurons. This theory received little criticism and was not contested much by other researchers prior to the 1890s. This is owing to the fact that the neural crest is quite closely related to the neural tube and thus this relationship makes sense. This discovery was made by His and Marshall, however, they found this out independently of one another.In the 1890s, Julia Platt, claimed that odontoblasts as well as the cartilages forming the facial and pharyngeal arch skeletons came from the ectoderm. This created much debate and was contested by many{{#pmid:22820859|PMID22820859}}. <br /> <br /> This is because this theory completely contradicted the germ-layer theory, whereby skeletal tissues originate at the mesoderm and not the ectoderm. The controversies this finding created brought about a slowing down of research, as demonstrated by a gap of almost 40 years between the theory that skeletal tissues originating from the neural crest. Today, it is known that the neural crest does indeed play a role in the development of the skeleton in vertebrates, particularly, the cranial neural crest. Although these studies were occurring, the focus was still primarily on researching pigment cells and ganglia of the spine up until the 1950s, when Sven Hörstadius' major work on the neural crest was published, titled "The Neural Crest: Its properties and derivatives in the light of experimental research". This work focused on experimental data tracing the development of the cartilaginous skeleton derived from the neural crest {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1960s - 1970s'''<br /> In the 1960s, the migration patterns of neural crest cells were studied in avian embryos (birds). This was a shift from studying the embryos of amphibians. This was inspired by studies conducted in the 1960s on neural crest cells migrating from the brain and spinal cord, known as trunk and cranial neural crest cells {{#pmid:19179766|PMID19179766}}. The cranial neural crest eventually becomes the bones, cartilage and connective tissues forming the foundation of the face, ears and teeth. The trunk neural crest cells can either become melanocytes or can migrate into sclerotomes which are later contributors to the cartilage of the spine and the dorsal root ganglia {{#pmid:22820859|PMID22820859}}. The cells in the trunk neural crest that migrate vertically become the sympathetic ganglia, the nerves proximal to the aorta and the adrenal medulla <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. In the 1970s many detailed maps signifying the pathways of many of the neural crest cells appeared as well as an understanding that the environment in which the neural crest cells are found plays a major role in their final development as well as the occurrences of abnormalities in the fetus {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1980s - 21st century'''<br /> [[File:Regions_of_NC_Cells.jpg|left|Neural crest regions|thumb|500px]]<br /> From the 1980s-1990s, the causative agent of organ transformation from one to another (homeotic patterning), as well as the Hox genes which regulate the axis of most symmetrical animal embryos were founded and studied. The neural crest, which previously was divided into the cranial and trunk regions, was now further divided into the vagal and sacral neural crest, the cardiac neural crest and the cephalic neural crest {{#pmid:19179766|PMID19179766}}. The vagal & sacral neural crest gives rise to the parasympathetic ganglia found in the gut. Without these ganglia, peristalsis, is not possible <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. The cardiac neural crest contributes to the valves, septa and major blood vessels of the heart, as well as connective tissues and cartilage{{#pmid:19179766|PMID19179766}}. This is important for the structure of the heart as well as its overall function, enabling it to move blood around the body efficiently as well as keep pulmonary and aortic circulation separated <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> <br /> <br /> Today, knowledge of the neural crest cells, their migration patterns, modes of differentiation, derivatives and apoptosis (cell death) are being studied extensively. This is being done on a comparative basis between different organisms, to add further evidence for evolution {{#pmid:19179766|PMID19179766}}. The neural crest is definitely forging a "crest" between the fields of developmental and evolutionary biology, as it is a structure '''shared exclusively by all vertebrates'''. Invertebrates do not derive their specialised cells from the neural crest as they do not have one, rather, they derive these from the endomesoderm {{#pmid:22230617|PMID22230617}}.<br /> <br /> '''Future directions'''<br /> <br /> Since its discovery by His, the neural crest field has made great progress, from studies performed on the structure, to analysis of the molecules and whether certain aspects of the neural crest are specific to a single species of organism, or to all vertebrates collectively. Future work on the cranial neural crest needs to be done as well as identifying and categorising the networks responsible for the proliferation and death of cells, as well as how the cells move and migrate, as well as the gene regulatory networks (GRNs) that regulate the synthesis of proteins. Advances in technology will undeniably lead us to more answers on the subject {{#pmid:22230617|PMID22230617}}.<br /> <br /> ===Developmental time course===<br /> ---- <br /> <br /> [[File:Adrenal_Medulla_Developmental_Timeline.jpg|right|thumb|500px]]<br /> <br /> The adrenal gland has two distinct sections, the cortex and the medulla, both with different embryonic origins. The cortex accounts for 90% of the adrenal glands and arises from intermediate mesoderm. The medulla only accounts for 10% of the adult adrenal glands, however it has neural crest embryonic origin. The medulla consists of chromaffinoblast cells which are migrant neuroblast cells from the neural crest, therefore the adrenal medulla is a component of the sympathetic nervous system.{{#pmid:21175739|PMID21175739}} Neural crest cells replicate in week 7 and begin to differentiate in week 8, the cells then migrate to the developing adrenal gland in week 9 of development.{{#pmid:25255746|PMID25255746}}{{#pmid:18279781|PMID18279781}} The neural crest cells infiltrate the cortex and the chromaffin cells are scattered islands in the cortex.{{#pmid:23354096|PMID23354096}} Throughout development the cells will become more compact in the centre of the gland, during this period of development the adrenal gland is growing rapidly. The gland is abnormally large until the second trimester and the medulla is much thicker prenatally.{{#pmid:18279781|PMID18279781}}{{#pmid:21175739|PMID21175739}}<br /> <br /> <br /> ===Embryonic origins===<br /> ----<br /> [[File:Trunk_NCC_migration.jpg|left|450px|thumb|Trunk NCC migration]]<br /> The adrenal gland is made up of the adrenal cortex and adrenal medulla, which both have different embryonic origins. The adrenal medulla arises from the neural crest tissue, found near the level of the coeliac plexus & sympathetic ganglion at somites 18-24 {{#pmid:16124976|PMID16124976}}. Specifically, this neural crest tissue comes from the trunk neural crest cells (see above figure to determine the approximate location in an embryo) <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> The trunk neural crest coordinates the development of the endocrine system, secretory cells, the peripheral nervous system and, to some degree, skeletal development, as well as innervation of the intestine {{#pmid: 28287247|PMID 28287247}}. The trunk neural cells arise caudally, undergo an epithelial to mesenchymal transition and follow three migratory pathways {{#pmid:20399766|PMID20399766}}.<br /> [[File:Differentiation_of_NCC.jpg|left|580px|thumb|Differentiation of chromaffin cells]]<br /> - A dorsolateral pathway (between ectoderm and somites), these become melanocytes, travel up to the point of the dermis and become a major part of the hair follicles and skin <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> - A ventrolateral pathway (through the somites)<br /> - A ventromedial pathway (between neural tube and posterior schlerotome){{#pmid:20399766|PMID20399766}}.<br /> <br /> Migration of neural crest cells from the sympathetic ganglion is what leads to the development of the adrenal medulla. In week 8 of development, immature cells called neuroblasts migrate through to the inner portion of the medulla, where they become the adrenal medulla {{#pmid:19683477|PMID19683477}}. Chromaffin cells are neuroendocrine cells and are found in the sympathetic ganglia and make up the majority of the adrenal medulla{{#pmid:19683477|PMID19683477}}. They synthesise and release a range of hormones in the body and arise from the temporary neural crest. The term chromaffin was inspired by the staining capacity of these cells when they came into contact with chrome salts. They make, store, export and use catecholamines, responsible for making noradrenaline and originate at the caudal region of somites 18-24 of the neural crest, also known as the adrenomedullary region {{#pmid:19683477|PMID19683477}}.<br /> <br /> For cells to leave the neural crest and begin their migration, certain conditions need to be met, that is, the cells need to be loosely connected, their tight junctions becoming relaxed, initiated by "Slug protein" and a loss of N-Cadherin which also leads to the loosening of these junctions. The surrounding matrix as well as chemotactic and stem cell factors of the neural tube are then what dictates how the neural crest cells move, some proteins stopping their migration to that area and others encouraging the movement <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. After splitting apart, the first neural crest cells move ventrally and pass into the spaces between the somites and then, through the anterior portions of each segment until they arrive at the para-aortic sites, where they become the cells of the sympathetic ganglia and the adrenal medulla {{#pmid:19683477|PMID19683477}}. BMP-4 (bone morphogenetic protein 4) then acts on these neural crest cells, preventing them from becoming cells that have a neural function and causing them to become chromaffin cells at the adrenal medulla. Glucocorticoids then play a role in maintenance of chromaffin cells in postnatal life, this was only found recently, as previously it was thought that glucocorticoids were responsible entirely for the differentiation of neural crest cells into chromaffin, or adrenomedullary cells {{#pmid:23220335|PMID23220335}}.<br /> <br /> ===Anatomy and Functions===<br /> <br /> ----<br /> <br /> ====Anatomy and Histology====<br /> <br /> The adrenal medulla makes up the inner section of the adrenal glands, and is surrounded by the cortex, and a connective tissue capsule. It lies in the centre of the gland and it rarely measures no more than 2mm in thickness {{#pmid:21107679|PMID21107679}}. The cells of the adrenal medulla are derived from the neural crest as opposed to the mesodermal origins of the cortex. The adrenal medulla contains secretory cells called chromaffin cells due to the agents they produce when oxidised, such as chromate {{#pmid:11215683|PMID11215683}}. These cells secrete epinephrine, norepinephrine, chromogranin and neuropeptides in response to various substances such as acetylcholine <ref name="PMID11215683"/>. [[File:ADRENAL MEDULLA .jpg|600px|thumb|right|Adrenal Medulla Histology]]<br /> <br /> There are many types of highly differentiated cells in the adult adrenal medulla: <br /> - Epinephrine cells (90% of all chromaffin cells) {{#pmid:24715564|PMID24715564}}<br /> - Norepinephrine cells (10% of all chromaffin cells) <ref name="PMID24715564"/><br /> - Small granule-containing cells (SGCs) <ref name="PMID11215683"/><br /> <br /> These cells also synthesise, store and secrete catecholamines through controlled and regulated pathways <ref name="PMID24715564"/>, such as various peptides like substance P and neurotensin.These cells have unique neuroendocrine characteristics as a result of their neural-crest origin. They receive preganglionic innervation by thoracic splanchnic nerves, and could almost be considered a specialised sympathetic ganglion. With postganglgionic bodies, cells of the medulla are densely clustered around their vasculature for the secretion of hormones into the bloodstream to moderate the concentration of epinephrine and norepinephrine. The adrenal medulla also contains presynaptic sympathetic ganglion cells <ref name="PMID11215683"/>. The small granule-containing cells are usually found in clusters whereas, the ganglion cells are found either individually or in clusters, usually dispersed among the chromaffin cells or among the nerve fibres {{#pmid:18021328|PMID18021328}}. During embryonic development (around weeks 9-12), in contrast to the developing adrenal cortex, the medulla does not show evidence of an organised structure other than a small cluster of cells scattered throughout its cortex {{#pmid:30247985|PMID30247985}}. <br /> <br /> <br /> <br /> ====Related Anatomy====<br /> <br /> The tissue and organ structure of the adrenal medulla should be understood with regard to its specialised function within the sympathetic nervous system. <br /> <br /> The medullary region of the adrenal glands is tasked with the endocrine secretions of adrenaline and nor-adrenaline in response to environmental stressors that are signalled for by the sympathetic nervous system. That is, the secretion of fight-or-flight response hormones in order to restrict vasculature to the trunk and increase vascular activity in the peripheral musculature.<br /> <br /> The adrenal glands are supplied by several branches of the great vessels in the abdominal cavity. The secreted catecholamines in the medulla are directly able to pass to the blood stream this way.<br /> <br /> These adrenal glands and their contents are retroperitoneal in the adult and varied in shape, with the left often being semilunar and right being pyramidal. Nervous supply of the adrenal glands is achieved by contributions from the splanchnic nerves of the celiac plexus. {{#pmid:11215683|PMID11215683}} <br /> <br /> [[File:Dd.jpg|400px|thumb|right|Adult Adrenal Glands in situ]] <br /> ----<br /> ====Role of the Adrenal Medulla====<br /> <br /> Understanding the biochemistry of catecholamines is necessary to see how the adrenal medulla is designed in the stages of embryology and how it is suited for life in the neonate and adult. <br /> <br /> The epinephrine and norepinephrine in the neonate and adult work by primarily changing the osmoregulatory state of vasculature in organs. With the exclusion of their neuromodulatory and neurotransmitter functions, epinephrine and norepinephrine are mainly tasked with the control of sympathetic and parasympathetic supplies. <br /> <br /> Norepinephrine is a constrictor of peripheral vasculature by antagonising the action of surface receptors expressed on the endothelium of blood vessels, specifically Alpha-1 and Alpha-2 receptors, such that vascular resistance increases. <br /> <br /> Epinephrine is both a vasoconstrictor and vasodilator, depending on what receptors it attaches to. As a non-selective adrenergic agonist, it acts on Alpha-1, Alpha-2, Beta-1, Beta-2 and Beta-3 receptors that are found throughout the body's tissues, yielding many different physiological responses. {{#pmid:19396395|PMID19396395}}<br /> <br /> '''Adult Function'''<br /> <br /> While the adrenal cortex releases glucocorticoids in response to long term stress, the adrenal medulla releases its hormones in response to short-term, acute stress. The adrenal medulla contains the neuroendocrine chromaffin cells which are responsible for secreting adrenaline and noradrenaline. The function of these hormones is primarily to maintain the body’s homeostasis, especially of the internal organs, and to properly activate the autonomic stress response, more commonly known as the ‘fight or flight’ response {{#pmid:30237243|PMID30237243}}. Thus the function of the medulla includes signalling the liver and skeletal muscles to convert glycogen into glucose for increased energy. This results in increased blood glucose levels. These hormones also increase the heart rate, pulse and blood pressure in preparation for the fight or flight response. In addition to this, these hormones dilate the lung airways and prompt vasodilation to further increase oxygenation of important organs such as the lung, brain and heart. Vasoconstriction of blood vessels is also prompted to other less essential organs such as the bladder and the digestive system.<br /> <br /> Other effects also include pupil dilation, dry mouth and a loss in peripheral vision <ref name="PMID18021328"/>. Paramount to the correct response of chromaffin cells is the synaptic connection of the preganglionic cells which originate from the central nervous system and project axons into the adrenal medulla. While this is a very important relationship, the mechanisms of this remains unknown <ref name="PMID30237243"/>. In addition to the release of catecholamines, cells in the medulla also release peptides through the process of exocytosis from chromaffin granules, to help regulate blood pressure and regulation throughout the body. These peptides also regulate the release of adrenaline and noradrenaline, blood vessel contraction and the immune response <ref name="PMID18021328"/>. <br /> <br /> '''Embryonic function'''<br /> <br /> The current knowledge about the development of the adrenal gland is limited, with nearly all models being from animals, and very limited functional data available from human fetal adrenals <ref name="PMID30247985"/>. Thus for these reasons, there is scarce information available on the embryonic adrenal medullary functions. Nevertheless, there is accumulating evidence that the catecholamines in the fetal adrenal medulla plays an important role in the time of delivery by controlling thermogenesis and heart regulation {{#pmid:6998630|PMID6998630}}. <br /> <br /> The hormones released by the medulla during birth also play a key role for the newborn’s adaptation to extrauterine life. Despite the immaturity of the adrenal medulla at birth, it is known that respiratory, metabolic and cardiovascular changes during delivery are dependent on the adrenomedullary hormones {{#pmid:3280659|PMID3280659}}. Experimental data from human and animal fetal research shows that the fetal sympathoadrenal system, consisting of the adrenal medulla, sympathetic neurons and chromaffin tissue work together to maintain fetal homeostasis {{#pmid:6346884|PMID6346884}}. The adrenal medulla thus appears to provide vital physiological functions for fetal and neonatal survival, especially during birth. <br /> <br /> <br /> ----<br /> <br /> ===Molecular mechanisms/factors/genes===<br /> ----<br /> <br /> ====Genes and Transcription Factors Involved with the Adrenal Medulla's Development====<br /> <br /> The 'story' of the Adrenal Medulla's neural crest tissue begins at the process of neurulation, the formation of the neural tube from the folding neural plate, which is comprised of developing ectoderm which is opposite to the primitive streak. It is here that several key chemical players are at work. The classic interpretation of Sonic Hedgehog (Shh) and Wnt signalling pathways as the only mediators here, has been shown to be incorrect. Research has uncovered other signallers such as: <br /> <br /> *Bone-Morphogenic-Protein-4 (BMP4) for the regional expression of nervous system distinctions in the growing neural plate. This maintains two important embryonic trancription factors known as Paired-Box (PAX) Genes 3 and 7 which can allow for expression of neural crest markers HNK-1, SRY-Box (SOX) 8, 9 and 10 as the neural tube closes and the neural crest delaminates from the folding. {{#pmid:16688176|PMID16688176}} <br /> <br /> *Slug via Wnt signalling, this allows for the loosening of gap junctions in the extracellular matrix surrounding the newly-formed neural tube and trunk of the embryo. This extracellular matrix has chemo-attractant molecules<br /> <br /> [[File:Catecholamine_Synthesis.jpg|400px|thumb|right|Biochemical Cascade of Catecholamine Synthesis]]<br /> <br /> The importance of Somitogenesis and Neural Crest come to a head when neural crest cells must migrate anteriorly past somites 18 to 24 <br /> <br /> Members of the SOX gene family have multiple key contributors to Neural Crest in the Adrenal Medulla.<br /> <br /> <br /> Mouse models have demonstrated that SOX-10 knock-outs (mice whose DNA has been engineered to not express SOX-10) do not have an adrenal medulla. There has also been suggestion that SOX-8,9 and 10 are all strongly related to the migratory patterning of neural crest cells to the developing adrenal glands. {{#pmid:18272785|PMID18272785}}<br /> <br /> The TH gene (for Tyrosine Hydroxylase) encodes the aforementioned enzyme in the adrenal medulla and central nervous system. Tyrosine Hydroxylase is crucial in biochemical pathways and cascades for the synthesis of catecholamines and other CNS neurotransmitters. The conversion from L-Tyrosine to L-DOPA is dependent upon the catalytic action of Tyrosine Hydroxylase. From there, L-DOPA can make Dopamine and eventually Epinephrine and Norepinephrine as well. {{#pmid:19396395|PMID19396395}}<br /> <br /> ===Abnormalities/abnormal development===<br /> ----<br /> <br /> Abnormalities of the Adrenal Medulla are much less common than its mesoderm-derived shell of the Adrenal Gland. Three of the most notorious abnormalities of the Adrenal Medulla include:<br /> <br /> * Pheochromocytomas<br /> * Ganglioneuromas<br /> * Neuroblastomas<br /> <br /> <br /> Pheochromocytomas (PCCs) are variable neoplasias of the adrenal medulla's chromaffin cells. There are many classifications of PCCs, with autosomal-dominant germ-line mutations and heredities being one of the main causes. Familial phaeochromocytoma-paraganglioma (PGL) syndromes exist, with PGL1 having mutations of the SDHD gene, PGL3 being mutated of the SDHC gene and PGL4 having mutation of the SDHB gene. These phenotypically present as extra-adrenal chromaffin bodies, malformation of the adrenal glands themselves, absence of chromaffin bodies and fluctuations in circulating catecholamines. {{#pmid:18021328|PMID18021328}}<br /> <br /> Ganglioneuromas (GNs) are classically-benign growths that are very rare and arise from neural crest tissue. They are not circumscribed to the adrenal medulla, but also are found in the sympathetic chain and trunk ganglia. As a result of their scarcity, not much is known about them other than a few aberrant genes and generic clinical presentations. ERBB3, the receptor tyrosine kinas is understood to be important in the development of GNs, as well as an extremely high prevalence of up-regulated GATA3. A key thing to note is also the '''lack''' of N-MYC expression in GNs, which is quite prominent in neuroblastomas and other neoplasias. {{#pmid:29085827|PMID29085827}} {{#pmid:23715162|PMID23715162}} <br /> <br /> Neuroblastomas (NBs) are a more aggressive form of cancer, derived from neuroblasts - the precursor cells to neurons. A rather common pediatric cancer, they are often in children who are in risk factor groups such as those with aforementioned familial cancer syndromes, neurofibromatosis-1. These tumours often present with extremely variable catecholamine concentrations, which has implications for blood pressure, heart contractility and much more. Urinary excretion of norepinephrine, homovanillic acid (HVA) and vanilmandelic acid (VMA) can be used to help diagnose a suspected lesion of the adrenal gland, as these chemicals are associated with altered chemical cascades that are suspicious of neuroblastic change. {{#pmid:16372223|PMID16372223}}<br /> <br /> <br /> Apart from these abnormalities, there are other pathologies that may be connected to the adrenal medulla. One such example is a pathology of the Organ of Zuckerkandl. Also known as the para-aortic body, the Organ of Zuckerkandl is a primarily-gestational organ comprised of chromaffin cells and serves a similar purpose to the adrenal medulla in neonatal life.<br /> <br /> ===Animal models===<br /> ----<br /> Animal models are an integral part of research in embryology. In particular due to the moral concerns regarding the use of humans in scientific research. As a result different animals are used as substitutes to simulate the same environments and hope to achieve results that would also be able to represent humans as well. Prenatal adrenal gland development has been described in a number of scientific reports dating from the 1900s to studies in more recent years. These involved a variety of animal models such as ox, sheep, swine and most commonly mice. <br /> <br /> ====Chromaffin cells====<br /> There has been extensive research conducted into the adrenal chromaffin cells and their embryological developments. As explained above nueral crest cells are pluripotent meaning they are able to differentiate into multiple different cells{{#pmid:19377845|PMID19377845}}. The neural crest cells give rise to chromaffin cells of the adrenal medulla.<br /> <br /> =====Rat Models=====<br /> [[File:Adrenal gland.png|300px|thumb|right|3D images showing TH - positive cells accumulating at the cranial and audal ends of the adrenal gland. A. A observation of adrenal gland and surrounding structures (at 17 days of gestation). B. Enhanced image to further focus on the dark TH - positive cells. C. Image with the other structures removed.]]<br /> Previous research has reported that nueral crest cells differentiate into chromaffin cells around 19 days of gestation before forming the adrenal medulla{{#pmid:28684471|PMID2868441}}. Past research had also suggested that neural crest derived adrenal gland cells migrate using the sympathetic ganglia to the adrenal gland or preaortic ganglion, following different pathways, to reach their specific destination. However the results have shown that the pathways used to reach its destinations overlapped. This would suggest that there is a possibility of the cells using the same pathway to move from the beginning production to the destination that is the adrenal medulla (for chromaffin cells) and the preaortic ganglion (other cells involved in the sympathetic system). <br /> <br /> One particular study done by M.Yamato in 2004, along with his fellow scientists attempted to study the migration of neural crest cells in Wistar rats. In order to observe the formation adrenal medulla from the neural crest cells during the embryonic period, Yamato used anti - tyrosine hydroxylase (TH) antiserum injected into the rat embryos between 13-17 days of gestation. The anti - TH antiserum stain allows the scientists to visualize the neural crest cells under a light microscope. Later three dimensional images were created. From the images observed between 13 to 15 days of gestation, the TH - positive cells can be seen to move from the dorsal to the adrenal primordium{{#pmid:15240937|PMID15240937}}. After 16 days it was observed that a capsule had formed in some parts and TH - positive cells had penetrated the adrenal gland{{#pmid:15240937|PMID15240937}}. At seventeen days, TH - positive cells can be seen collecting at the medial part of the adrenal gland. The reconstructed images also shows that at the later stages during the 16-17 days of gestation, the accumulation of TH - positive cells grow and in combination with cell division leads to the formation of the adrenal medulla.<br /> <br /> =====Chicken models=====<br /> Chicken and rat models are often the most commonly used models when dealing with neural crest cells. In this particular review, collates multiple researchers results and presents evidence to discuss previous information suggesting that sympathetic neurons and chromaffin cells do not share a common progenitor{{#pmid:3693940|PMID3693940}}. The relevant study involved the use of cell cultures, Sympathoadrneal (SA) progenitor cells from embryonic(from chick embryos) and eary developmental stages were able to be procured. From these cultures it was easy to identify that glucocorticoids were crucial in the differentiation of SA cells into their derivatives, sympathetic neurons and chromaffin cells.<br /> <br /> [[File:Expression of BMP protein 4 .jpg|300px|thumb|right|Expression of BMP - 4 in the adrenal cortex at developmental stages. Shows the movement of the chromaffin progenitors moving from each stage of development. A-D: collection of progenitors outside E-H: cells have begun to penetrate the adrenal cortical region I-L: chromaffin cells have completely intergrated intergreted within the gland sg: sympathetic ganglia ac:adrenal cortical region ag: adrenal gland da: dorsal aortic region]]<br /> <br /> Another study conducted deals with the role of the bone morphogenetic protein(BMP-4) and its importance in the development of the adrenal medullary cells, chromaffin cells{{#pmid:18945349|PMID18945349}}. Previous research had shown that BMP - 4 a growth factor is plays an important role in the regulation of chromaffin cell production{{#pmid:10679774|PMID10679774}}. The researchers incubated chick embryos for 3 - 9 embryonic days and dissected them to be used for tissue cultures. Embryonic day 8 chick embryos had BMP - 4 overexpressing cells implanted in the sympathetic ganglia area, as well as other neurons which contained chromaffin like cells. What was observed was an increase in size and numbers of 'chromaffin' granules{{#pmid:18945349|PMID18945349}}. As a result it was concluded that although BMP - 4 promotes certain chromaffin traits, it does not have the capability to convert sympathetic neurons into a chromaffin type cell.<br /> <br /> ===Current research (labs)===<br /> ----<br /> <br /> ==== Generation of Adrenal Chromaffin-like Cells from Human Pluripotent Stem Cells====<br /> <br /> As explained above the adrenal medulla plays an important part in the autonomic system of an adult human. The chromaffin cells, in particular, are important neural crest derived cell that is closely related to the adrenal medulla. Previous findings have focused specifically on the mechanisms controlling the NCC migration and how these cells go on to form the different derivatives in their particular destinations in the embryo. For example, as previously explained studies have shown that chromaffin cells have been observed to move to the adrenal gland to form the medulla of the adrenal gland. This report goes through a recent study that involves the adrenal medullary cells, in particular chromaffin cells, and their potential to be used to model certain pathological diseases related to these cells. This is part of a study that also involves neural crest cells and their ability to differentiate into multiple different types of cells<ref>Lumb, R., & Schwarz, Q. (2015). Sympathoadrenal neural crest cells: The known, unknown and forgotten?. Development, Growth & Differentiation, 57(2), 146-157. doi: 10.1111/dgd.12189</ref>. Neural crest cells and SAPs from human embryonic cells and induced pluripotent stem cells were generated to be used in the experiment. By exposing the pluripotent stem cells to BMP4 in vitro, results showed that these cells would 'upregulate' the chromaffin cell - specific marker PMNT (an enzyme that synthesizes adrenaline). Furthermore when the cells from human embryos were implanted into avian embryos, there was a visible potential for the human cells to differentiate into cells that expressed the chromaffin cell markers{{#pmid:5768882|PMID5768882}}.<br /> <br /> <br /> ====Multipotent Peripheral Glial Cells Generate Neuroendocrine Cells of the Adrenal Medulla====<br /> <br /> Similar to the first study, this one also focuses on the chromaffin cells and their relationship to the adrenal medulla. Chromaffin cells often represent the main endocrine component that is believed to differentiate from neural crest cells{{#pmid:28684471|PMID28684471}}. The study focuses specifically on the idea that previous research has suggested that nerve - associated schwann cell precursor is a progenitor of chromaffin cells. What the findings suggested was that peripheral nerves provided migration routes for the progenitors. This is backed up by the results, a high concentration of chromaffin cells can be found being derived from the nerve, as nerve ablated mice in the experiment showed a large difference of 78% less cells compared to the control. Other than this, the study also brought to light the proliferative potential of the cells from nerves, with different other cell types being discovered as well (including cells such as parasympathetic{{#pmid:24925912|PMID24925912}} and melanocytes {{#pmid:19837037 |PMID19837037}}). The findings would provide useful information into further understanding the adrenal gland and its embryonic origins (as there is still much to learn regarding the formation of the adrenal medulla) but also pathological diseases such as neuroblastoma and pheochromatocytoma which are most common in the adrenal glandular region {{#pmid:23106811|PMID23106811}}.<br /> <br /> ===Glossary===<br /> ----<br /> ===Reference list===</div>

Z5091101 https://embryology.med.unsw.edu.au/embryology/index.php?title=2018_Group_Project_1&diff=358291 2018 Group Project 1 2018-10-16T00:38:46Z

<p>Z5091101: /* History */</p> <hr /> <div>=The Contribution of Neural Crest Cells to the Adrenal Medulla=<br /> ----<br /> {{2018ANAT2341ProjectHeader}}<br /> <br /> <br /> ===Introduction===<br /> <br /> ----<br /> <br /> The neural crest of an embryo migrates and differentiates to form various components of the body. This transient population of pluripotent stem-cells give rise to many complex and different structures across the adult by chemical signalling. One of these tissues is the medulla of the adrenal gland which is involved in the production of epinephrine and norepinephrine. This project will comprehensively outline the history of neural crest research, the embryonic developmental time course, tissue and organ structure, molecular mechanisms, abnormalities, animal models and current research.<br /> <br /> ===History===<br /> ----<br /> '''Describing the neural crest'''<br /> [[File:Wilhelm_His_History_Wilhelm.jpeg|left|230px|thumb|Wilhelm His]]<br /> The "neural crest" is a structure in the embryo and is the junction between the neural and epidermal ectoderm. It is exclusive to vertebrates and forms a range of structures{{#pmid:22230617|PMID22230617}}. The neural crest contributes a large number of cells of varying structure and function that directly or indirectly contribute to the development of tissues and organs within the body {{#pmid:19179766|PMID19179766}}. In 1868, the neural crest cells were first identified in a chick embryo as a collection of cells known as "Zwischenstrang" by Professor Wilhelm His {{#pmid:22820859|PMID22820859}}. Wilhelm His was among the first to provide an explanation for the mechanics governing the developing embryo as well as the physiology and the organs that the differing germinal regions would eventually give rise to. In 1878, the term neural ridge was used to describe this collection of cells but the term neural crest was later coined by Arthur Milnes Marshall in 1879 in a paper he worked on disseminating the knowledge from his research on the development of cranial nerves in chicken embryos. {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1890s-1950s'''<br /> The neural crest is the point of origin for spinal/cranial ganglia and neurons. This theory received little criticism and was not contested much by other researchers prior to the 1890s. This is owing to the fact that the neural crest is quite closely related to the neural tube and thus this relationship makes sense. This discovery was made by His and Marshall, however, they found this out independently of one another.In the 1890s, Julia Platt, claimed that odontoblasts as well as the cartilages forming the facial and pharyngeal arch skeletons came from the ectoderm. This created much debate and was contested by many{{#pmid:22820859|PMID22820859}}. <br /> <br /> This is because this theory completely contradicted the germ-layer theory, whereby skeletal tissues originate at the mesoderm and not the ectoderm. The controversies this finding created brought about a slowing down of research, as demonstrated by a gap of almost 40 years between the theory that skeletal tissues originating from the neural crest. Today, it is known that the neural crest does indeed play a role in the development of the skeleton in vertebrates, particularly, the cranial neural crest. Although these studies were occurring, the focus was still primarily on researching pigment cells and ganglia of the spine up until the 1950s, when Sven Hörstadius' major work on the neural crest was published, titled "The Neural Crest: Its properties and derivatives in the light of experimental research". This work focused on experimental data tracing the development of the cartilaginous skeleton derived from the neural crest {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1960s - 1970s'''<br /> In the 1960s, the migration patterns of neural crest cells were studied in avian embryos (birds). This was a shift from studying the embryos of amphibians. This was inspired by studies conducted in the 1960s on neural crest cells migrating from the brain and spinal cord, known as trunk and cranial neural crest cells {{#pmid:19179766|PMID19179766}}. The cranial neural crest eventually becomes the bones, cartilage and connective tissues forming the foundation of the face, ears and teeth. The trunk neural crest cells can either become melanocytes or can migrate into sclerotomes which are later contributors to the cartilage of the spine and the dorsal root ganglia {{#pmid:22820859|PMID22820859}}. The cells in the trunk neural crest that migrate vertically become the sympathetic ganglia, the nerves proximal to the aorta and the adrenal medulla <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. In the 1970s many detailed maps signifying the pathways of many of the neural crest cells appeared as well as an understanding that the environment in which the neural crest cells are found plays a major role in their final development as well as the occurrences of abnormalities in the fetus {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1980s - 21st century'''<br /> [[File:Regions_of_NC_Cells.jpg|left|Neural crest regions|thumb|500px]]<br /> From the 1980s-1990s, the causative agent of organ transformation from one to another (homeotic patterning), as well as the Hox genes which regulate the axis of most symmetrical animal embryos were founded and studied. The neural crest, which previously was divided into the cranial and trunk regions, was now further divided into the vagal and sacral neural crest, the cardiac neural crest and the cephalic neural crest {{#pmid:19179766|PMID19179766}}. The vagal & sacral neural crest gives rise to the parasympathetic ganglia found in the gut. Without these ganglia, peristalsis, is not possible <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. The cardiac neural crest contributes to the valves, septa and major blood vessels of the heart, as well as connective tissues and cartilage{{#pmid:19179766|PMID19179766}}. This is important for the structure of the heart as well as its overall function, enabling it to move blood around the body efficiently as well as keep pulmonary and aortic circulation separated <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> <br /> <br /> Today, knowledge of the neural crest cells, their migration patterns, modes of differentiation, derivatives and apoptosis (cell death) are being studied extensively. This is being done on a comparative basis between different organisms, to add further evidence for evolution {{#pmid:19179766|PMID19179766}}. The neural crest is definitely forging a "crest" between the fields of developmental and evolutionary biology, as it is a structure '''shared exclusively by all vertebrates'''. Invertebrates do not derive their specialised cells from the neural crest as they do not have one, rather, they derive these from the endomesoderm {{#pmid:22230617|PMID22230617}}.<br /> <br /> '''Future directions'''<br /> <br /> Since its discovery by His, the neural crest field has made great progress, from studies performed on the structure, to analysis of the molecules and whether certain aspects of the neural crest are specific to a single species of organism, or to all vertebrates collectively. Future work on the cranial neural crest needs to be done as well as identifying and categorising the networks responsible for the proliferation and death of cells, as well as how the cells move and migrate, as well as the gene regulatory networks (GRNs) that regulate the synthesis of proteins. Advances in technology will undeniably lead us to more answers on the subject {{#pmid:22230617|PMID22230617}}.<br /> <br /> ===Developmental time course===<br /> ---- <br /> <br /> [[File:Adrenal_Medulla_Developmental_Timeline.jpg|right|thumb|500px]]<br /> <br /> The adrenal gland has two distinct sections, the cortex and the medulla, both with different embryonic origins. The cortex accounts for 90% of the adrenal glands and arises from intermediate mesoderm. The medulla only accounts for 10% of the adult adrenal glands, however it has neural crest embryonic origin. The medulla consists of chromaffinoblast cells which are migrant neuroblast cells from the neural crest, therefore the adrenal medulla is a component of the sympathetic nervous system.{{#pmid:21175739|PMID21175739}} Neural crest cells replicate in week 7 and begin to differentiate in week 8, the cells then migrate to the developing adrenal gland in week 9 of development.{{#pmid:25255746|PMID25255746}}{{#pmid:18279781|PMID18279781}} The neural crest cells infiltrate the cortex and the chromaffin cells are scattered islands in the cortex.{{#pmid:23354096|PMID23354096}} Throughout development the cells will become more compact in the centre of the gland, during this period of development the adrenal gland is growing rapidly. The gland is abnormally large until the second trimester and the medulla is much thicker prenatally.{{#pmid:18279781|PMID18279781}}{{#pmid:21175739|PMID21175739}}<br /> <br /> <br /> ===Embryonic origins===<br /> ----<br /> [[File:Trunk_NCC_migration.jpg|left|450px|thumb|Trunk NCC migration]]<br /> The adrenal gland is made up of the adrenal cortex and adrenal medulla, which both have different embryonic origins. The adrenal medulla arises from the neural crest tissue, found near the level of the coeliac plexus & sympathetic ganglion at somites 18-24 {{#pmid:16124976|PMID16124976}}. Specifically, this neural crest tissue comes from the trunk neural crest cells (see above figure to determine the approximate location in an embryo) <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> The trunk neural crest coordinates the development of the endocrine system, secretory cells, the peripheral nervous system and, to some degree, skeletal development, as well as innervation of the intestine {{#pmid: 28287247|PMID 28287247}}. The trunk neural cells arise caudally, undergo an epithelial to mesenchymal transition and follow three migratory pathways {{#pmid:20399766|PMID20399766}}.<br /> [[File:Differentiation_of_NCC.jpg|left|580px|thumb|Differentiation of chromaffin cells]]<br /> - A dorsolateral pathway (between ectoderm and somites), these become melanocytes, travel up to the point of the dermis and become a major part of the hair follicles and skin <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> - A ventrolateral pathway (through the somites)<br /> - A ventromedial pathway (between neural tube and posterior schlerotome){{#pmid:20399766|PMID20399766}}.<br /> <br /> Migration of neural crest cells from the sympathetic ganglion is what leads to the development of the adrenal medulla. In week 8 of development, immature cells called neuroblasts migrate through to the inner portion of the medulla, where they become the adrenal medulla {{#pmid:19683477|PMID19683477}}. Chromaffin cells are neuroendocrine cells and are found in the sympathetic ganglia and make up the majority of the adrenal medulla{{#pmid:19683477|PMID19683477}}. They synthesise and release a range of hormones in the body and arise from the temporary neural crest. The term chromaffin was inspired by the staining capacity of these cells when they came into contact with chrome salts. They make, store, export and use catecholamines, responsible for making noradrenaline and originate at the caudal region of somites 18-24 of the neural crest, also known as the adrenomedullary region {{#pmid:19683477|PMID19683477}}.<br /> <br /> For cells to leave the neural crest and begin their migration, certain conditions need to be met, that is, the cells need to be loosely connected, their tight junctions becoming relaxed, initiated by "Slug protein" and a loss of N-Cadherin which also leads to the loosening of these junctions. The surrounding matrix as well as chemotactic and stem cell factors of the neural tube are then what dictates how the neural crest cells move, some proteins stopping their migration to that area and others encouraging the movement <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. After splitting apart, the first neural crest cells move ventrally and pass into the spaces between the somites and then, through the anterior portions of each segment until they arrive at the para-aortic sites, where they become the cells of the sympathetic ganglia and the adrenal medulla {{#pmid:19683477|PMID19683477}}. BMP-4 (bone morphogenetic protein 4) then acts on these neural crest cells, preventing them from becoming cells that have a neural function and causing them to become chromaffin cells at the adrenal medulla. Glucocorticoids then play a role in maintenance of chromaffin cells in postnatal life, this was only found recently, as previously it was thought that glucocorticoids were responsible entirely for the differentiation of neural crest cells into chromaffin, or adrenomedullary cells {{#pmid:23220335|PMID23220335}}.<br /> <br /> ===Anatomy and Functions===<br /> <br /> ----<br /> <br /> ====Anatomy and Histology====<br /> <br /> The adrenal medulla makes up the inner section of the adrenal glands, and is surrounded by the cortex, and a connective tissue capsule. It lies in the centre of the gland and it rarely measures no more than 2mm in thickness {{#pmid:21107679|PMID21107679}}. The cells of the adrenal medulla are derived from the neural crest as opposed to the mesodermal origins of the cortex. The adrenal medulla contains secretory cells called chromaffin cells due to the agents they produce when oxidised, such as chromate {{#pmid:11215683|PMID11215683}}. These cells secrete epinephrine, norepinephrine, chromogranin and neuropeptides in response to various substances such as acetylcholine <ref name="PMID11215683"/>. [[File:ADRENAL MEDULLA .jpg|600px|thumb|right|Adrenal Medulla Histology]]<br /> <br /> There are many types of highly differentiated cells in the adult adrenal medulla: <br /> - Epinephrine cells (90% of all chromaffin cells) {{#pmid:24715564|PMID24715564}}<br /> - Norepinephrine cells (10% of all chromaffin cells) <ref name="PMID24715564"/><br /> - Small granule-containing cells (SGCs) <ref name="PMID11215683"/><br /> <br /> These cells also synthesise, store and secrete catecholamines through controlled and regulated pathways <ref name="PMID24715564"/>, such as various peptides like substance P and neurotensin.These cells have unique neuroendocrine characteristics as a result of their neural-crest origin. They receive preganglionic innervation by thoracic splanchnic nerves, and could almost be considered a specialised sympathetic ganglion. With postganglgionic bodies, cells of the medulla are densely clustered around their vasculature for the secretion of hormones into the bloodstream to moderate the concentration of epinephrine and norepinephrine. The adrenal medulla also contains presynaptic sympathetic ganglion cells <ref name="PMID11215683"/>. The small granule-containing cells are usually found in clusters whereas, the ganglion cells are found either individually or in clusters, usually dispersed among the chromaffin cells or among the nerve fibres {{#pmid:18021328|PMID18021328}}. During embryonic development (around weeks 9-12), in contrast to the developing adrenal cortex, the medulla does not show evidence of an organised structure other than a small cluster of cells scattered throughout its cortex {{#pmid:30247985|PMID30247985}}. <br /> <br /> <br /> <br /> ====Related Anatomy====<br /> <br /> The tissue and organ structure of the adrenal medulla should be understood with regard to its specialised function within the sympathetic nervous system. <br /> <br /> The medullary region of the adrenal glands is tasked with the endocrine secretions of adrenaline and nor-adrenaline in response to environmental stressors that are signalled for by the sympathetic nervous system. That is, the secretion of fight-or-flight response hormones in order to restrict vasculature to the trunk and increase vascular activity in the peripheral musculature.<br /> <br /> The adrenal glands are supplied by several branches of the great vessels in the abdominal cavity. The secreted catecholamines in the medulla are directly able to pass to the blood stream this way.<br /> <br /> These adrenal glands and their contents are retroperitoneal in the adult and varied in shape, with the left often being semilunar and right being pyramidal. Nervous supply of the adrenal glands is achieved by contributions from the splanchnic nerves of the celiac plexus. {{#pmid:11215683|PMID11215683}} <br /> <br /> [[File:Dd.jpg|400px|thumb|right|Adult Adrenal Glands in situ]] <br /> ----<br /> ====Role of the Adrenal Medulla====<br /> <br /> Understanding the biochemistry of catecholamines is necessary to see how the adrenal medulla is designed in the stages of embryology and how it is suited for life in the neonate and adult. <br /> <br /> The epinephrine and norepinephrine in the neonate and adult work by primarily changing the osmoregulatory state of vasculature in organs. With the exclusion of their neuromodulatory and neurotransmitter functions, epinephrine and norepinephrine are mainly tasked with the control of sympathetic and parasympathetic supplies. <br /> <br /> Norepinephrine is a constrictor of peripheral vasculature by antagonising the action of surface receptors expressed on the endothelium of blood vessels, specifically Alpha-1 and Alpha-2 receptors, such that vascular resistance increases. <br /> <br /> Epinephrine is both a vasoconstrictor and vasodilator, depending on what receptors it attaches to. As a non-selective adrenergic agonist, it acts on Alpha-1, Alpha-2, Beta-1, Beta-2 and Beta-3 receptors that are found throughout the body's tissues, yielding many different physiological responses. {{#pmid:19396395|PMID19396395}}<br /> <br /> '''Adult Function'''<br /> <br /> While the adrenal cortex releases glucocorticoids in response to long term stress, the adrenal medulla releases its hormones in response to short-term, acute stress. The adrenal medulla contains the neuroendocrine chromaffin cells which are responsible for secreting adrenaline and noradrenaline. The function of these hormones is primarily to maintain the body’s homeostasis, especially of the internal organs, and to properly activate the autonomic stress response, more commonly known as the ‘fight or flight’ response {{#pmid:30237243|PMID30237243}}. Thus the function of the medulla includes signalling the liver and skeletal muscles to convert glycogen into glucose for increased energy. This results in increased blood glucose levels. These hormones also increase the heart rate, pulse and blood pressure in preparation for the fight or flight response. In addition to this, these hormones dilate the lung airways and prompt vasodilation to further increase oxygenation of important organs such as the lung, brain and heart. Vasoconstriction of blood vessels is also prompted to other less essential organs such as the bladder and the digestive system.<br /> <br /> Other effects also include pupil dilation, dry mouth and a loss in peripheral vision <ref name="PMID18021328"/>. Paramount to the correct response of chromaffin cells is the synaptic connection of the preganglionic cells which originate from the central nervous system and project axons into the adrenal medulla. While this is a very important relationship, the mechanisms of this remains unknown <ref name="PMID30237243"/>. In addition to the release of catecholamines, cells in the medulla also release peptides through the process of exocytosis from chromaffin granules, to help regulate blood pressure and regulation throughout the body. These peptides also regulate the release of adrenaline and noradrenaline, blood vessel contraction and the immune response <ref name="PMID18021328"/>. <br /> <br /> '''Embryonic function'''<br /> <br /> The current knowledge about the development of the adrenal gland is limited, with nearly all models being from animals, and very limited functional data available from human fetal adrenals <ref name="PMID30247985"/>. Thus for these reasons, there is scarce information available on the embryonic adrenal medullary functions. Nevertheless, there is accumulating evidence that the catecholamines in the fetal adrenal medulla plays an important role in the time of delivery by controlling thermogenesis and heart regulation {{#pmid:6998630|PMID6998630}}. <br /> <br /> The hormones released by the medulla during birth also play a key role for the newborn’s adaptation to extrauterine life. Despite the immaturity of the adrenal medulla at birth, it is known that respiratory, metabolic and cardiovascular changes during delivery are dependent on the adrenomedullary hormones {{#pmid:3280659|PMID3280659}}. Experimental data from human and animal fetal research shows that the fetal sympathoadrenal system, consisting of the adrenal medulla, sympathetic neurons and chromaffin tissue work together to maintain fetal homeostasis {{#pmid:6346884|PMID6346884}}. The adrenal medulla thus appears to provide vital physiological functions for fetal and neonatal survival, especially during birth. <br /> <br /> <br /> ----<br /> <br /> ===Molecular mechanisms/factors/genes===<br /> ----<br /> <br /> ====Genes and Transcription Factors Involved with the Adrenal Medulla's Development====<br /> <br /> The 'story' of the Adrenal Medulla's neural crest tissue begins at the process of neurulation, the formation of the neural tube from the folding neural plate, which is comprised of developing ectoderm which is opposite to the primitive streak. It is here that several key chemical players are at work. The classic interpretation of Sonic Hedgehog (Shh) and Wnt signalling pathways as the only mediators here, has been shown to be incorrect. Research has uncovered other signallers such as: <br /> <br /> *Bone-Morphogenic-Protein-4 (BMP4) for the regional expression of nervous system distinctions in the growing neural plate. This maintains two important embryonic trancription factors known as Paired-Box (PAX) Genes 3 and 7 which can allow for expression of neural crest markers HNK-1, SRY-Box (SOX) 8, 9 and 10 as the neural tube closes and the neural crest delaminates from the folding. {{#pmid:16688176|PMID16688176}} <br /> <br /> *Slug via Wnt signalling, this allows for the loosening of gap junctions in the extracellular matrix surrounding the newly-formed neural tube and trunk of the embryo. This extracellular matrix has chemo-attractant molecules<br /> <br /> [[File:Catecholamine_Synthesis.jpg|400px|thumb|right|Biochemical Cascade of Catecholamine Synthesis]]<br /> <br /> The importance of Somitogenesis and Neural Crest come to a head when neural crest cells must migrate anteriorly past somites 18 to 24 <br /> <br /> Members of the SOX gene family have multiple key contributors to Neural Crest in the Adrenal Medulla.<br /> <br /> <br /> Mouse models have demonstrated that SOX-10 knock-outs (mice whose DNA has been engineered to not express SOX-10) do not have an adrenal medulla. There has also been suggestion that SOX-8,9 and 10 are all strongly related to the migratory patterning of neural crest cells to the developing adrenal glands. {{#pmid:18272785|PMID18272785}}<br /> <br /> The TH gene (for Tyrosine Hydroxylase) encodes the aforementioned enzyme in the adrenal medulla and central nervous system. Tyrosine Hydroxylase is crucial in biochemical pathways and cascades for the synthesis of catecholamines and other CNS neurotransmitters. The conversion from L-Tyrosine to L-DOPA is dependent upon the catalytic action of Tyrosine Hydroxylase. From there, L-DOPA can make Dopamine and eventually Epinephrine and Norepinephrine as well. {{#pmid:19396395|PMID19396395}}<br /> <br /> ===Abnormalities/abnormal development===<br /> ----<br /> <br /> Abnormalities of the Adrenal Medulla are much less common than its mesoderm-derived shell of the Adrenal Gland. Three of the most notorious abnormalities of the Adrenal Medulla include:<br /> <br /> * Pheochromocytomas<br /> * Ganglioneuromas<br /> * Neuroblastomas<br /> <br /> <br /> Pheochromocytomas (PCCs) are variable neoplasias of the adrenal medulla's chromaffin cells. There are many classifications of PCCs, with autosomal-dominant germ-line mutations and heredities being one of the main causes. Familial phaeochromocytoma-paraganglioma (PGL) syndromes exist, with PGL1 having mutations of the SDHD gene, PGL3 being mutated of the SDHC gene and PGL4 having mutation of the SDHB gene. These phenotypically present as extra-adrenal chromaffin bodies, malformation of the adrenal glands themselves, absence of chromaffin bodies and fluctuations in circulating catecholamines. {{#pmid:18021328|PMID18021328}}<br /> <br /> Ganglioneuromas (GNs) are classically-benign growths that are very rare and arise from neural crest tissue. They are not circumscribed to the adrenal medulla, but also are found in the sympathetic chain and trunk ganglia. As a result of their scarcity, not much is known about them other than a few aberrant genes and generic clinical presentations. ERBB3, the receptor tyrosine kinas is understood to be important in the development of GNs, as well as an extremely high prevalence of up-regulated GATA3. A key thing to note is also the '''lack''' of N-MYC expression in GNs, which is quite prominent in neuroblastomas and other neoplasias. {{#pmid:29085827|PMID29085827}} {{#pmid:23715162|PMID23715162}} <br /> <br /> Neuroblastomas (NBs) are a more aggressive form of cancer, derived from neuroblasts - the precursor cells to neurons. A rather common pediatric cancer, they are often in children who are in risk factor groups such as those with aforementioned familial cancer syndromes, neurofibromatosis-1. These tumours often present with extremely variable catecholamine concentrations, which has implications for blood pressure, heart contractility and much more. Urinary excretion of norepinephrine, homovanillic acid (HVA) and vanilmandelic acid (VMA) can be used to help diagnose a suspected lesion of the adrenal gland, as these chemicals are associated with altered chemical cascades that are suspicious of neuroblastic change. {{#pmid:16372223|PMID16372223}}<br /> <br /> <br /> Apart from these abnormalities, there are other pathologies that may be connected to the adrenal medulla. One such example is a pathology of the Organ of Zuckerkandl. Also known as the para-aortic body, the Organ of Zuckerkandl is a primarily-gestational organ comprised of chromaffin cells and serves a similar purpose to the adrenal medulla in neonatal life.<br /> <br /> ===Animal models===<br /> ----<br /> Animal models are an integral part of research in embryology. In particular due to the moral concerns regarding the use of humans in scientific research. As a result different animals are used as substitutes to simulate the same environments and hope to achieve results that would also be able to represent humans as well. Prenatal adrenal gland development has been described in a number of scientific reports dating from the 1900s to studies in more recent years. These involved a variety of animal models such as ox, sheep, swine and most commonly mice. <br /> <br /> ====Chromaffin cells====<br /> There has been extensive research conducted into the adrenal chromaffin cells and their embryological developments. As explained above nueral crest cells are pluripotent meaning they are able to differentiate into multiple different cells{{#pmid:19377845|PMID19377845}}. The neural crest cells give rise to chromaffin cells of the adrenal medulla.<br /> <br /> =====Rat Models=====<br /> [[File:Adrenal gland.png|300px|thumb|right|3D images showing TH - positive cells accumulating at the cranial and audal ends of the adrenal gland. A. A observation of adrenal gland and surrounding structures (at 17 days of gestation). B. Enhanced image to further focus on the dark TH - positive cells. C. Image with the other structures removed.]]<br /> Previous research has reported that nueral crest cells differentiate into chromaffin cells around 19 days of gestation before forming the adrenal medulla{{#pmid:28684471|PMID2868441}}. Past research had also suggested that neural crest derived adrenal gland cells migrate using the sympathetic ganglia to the adrenal gland or preaortic ganglion, following different pathways, to reach their specific destination. However the results have shown that the pathways used to reach its destinations overlapped. This would suggest that there is a possibility of the cells using the same pathway to move from the beginning production to the destination that is the adrenal medulla (for chromaffin cells) and the preaortic ganglion (other cells involved in the sympathetic system). <br /> <br /> One particular study done by M.Yamato in 2004, along with his fellow scientists attempted to study the migration of neural crest cells in Wistar rats. In order to observe the formation adrenal medulla from the neural crest cells during the embryonic period, Yamato used anti - tyrosine hydroxylase (TH) antiserum injected into the rat embryos between 13-17 days of gestation. The anti - TH antiserum stain allows the scientists to visualize the neural crest cells under a light microscope. Later three dimensional images were created. From the images observed between 13 to 15 days of gestation, the TH - positive cells can be seen to move from the dorsal to the adrenal primordium{{#pmid:15240937|PMID15240937}}. After 16 days it was observed that a capsule had formed in some parts and TH - positive cells had penetrated the adrenal gland{{#pmid:15240937|PMID15240937}}. At seventeen days, TH - positive cells can be seen collecting at the medial part of the adrenal gland. The reconstructed images also shows that at the later stages during the 16-17 days of gestation, the accumulation of TH - positive cells grow and in combination with cell division leads to the formation of the adrenal medulla.<br /> <br /> =====Chicken models=====<br /> Chicken and rat models are often the most commonly used models when dealing with neural crest cells. In this particular review, collates multiple researchers results and presents evidence to discuss previous information suggesting that sympathetic neurons and chromaffin cells do not share a common progenitor{{#pmid:3693940|PMID3693940}}. The relevant study involved the use of cell cultures, Sympathoadrneal (SA) progenitor cells from embryonic(from chick embryos) and eary developmental stages were able to be procured. From these cultures it was easy to identify that glucocorticoids were crucial in the differentiation of SA cells into their derivatives, sympathetic neurons and chromaffin cells.<br /> <br /> [[File:Expression of BMP protein 4 .jpg|300px|thumb|right|Expression of BMP - 4 in the adrenal cortex at developmental stages. Shows the movement of the chromaffin progenitors moving from each stage of development. A-D: collection of progenitors outside E-H: cells have begun to penetrate the adrenal cortical region I-L: chromaffin cells have completely intergrated intergreted within the gland sg: sympathetic ganglia ac:adrenal cortical region ag: adrenal gland da: dorsal aortic region]]<br /> <br /> Another study conducted deals with the role of the bone morphogenetic protein(BMP-4) and its importance in the development of the adrenal medullary cells, chromaffin cells{{#pmid:18945349|PMID18945349}}. Previous research had shown that BMP - 4 a growth factor is plays an important role in the regulation of chromaffin cell production{{#pmid:10679774|PMID10679774}}. The researchers incubated chick embryos for 3 - 9 embryonic days and dissected them to be used for tissue cultures. Embryonic day 8 chick embryos had BMP - 4 overexpressing cells implanted in the sympathetic ganglia area, as well as other neurons which contained chromaffin like cells. What was observed was an increase in size and numbers of 'chromaffin' granules{{#pmid:18945349|PMID18945349}}. As a result it was concluded that although BMP - 4 promotes certain chromaffin traits, it does not have the capability to convert sympathetic neurons into a chromaffin type cell.<br /> <br /> ===Current research (labs)===<br /> ----<br /> <br /> ==== Generation of Adrenal Chromaffin-like Cells from Human Pluripotent Stem Cells====<br /> <br /> As explained above the adrenal medulla plays an important part in the autonomic system of an adult human. The chromaffin cells, in particular, are important neural crest derived cell that is closely related to the adrenal medulla. Previous findings have focused specifically on the mechanisms controlling the NCC migration and how these cells go on to form the different derivatives in their particular destinations in the embryo. For example, as previously explained studies have shown that chromaffin cells have been observed to move to the adrenal gland to form the medulla of the adrenal gland. This report goes through a recent study that involves the adrenal medullary cells, in particular chromaffin cells, and their potential to be used to model certain pathological diseases related to these cells. This is part of a study that also involves neural crest cells and their ability to differentiate into multiple different types of cells<ref>Lumb, R., & Schwarz, Q. (2015). Sympathoadrenal neural crest cells: The known, unknown and forgotten?. Development, Growth & Differentiation, 57(2), 146-157. doi: 10.1111/dgd.12189</ref>. Neural crest cells and SAPs from human embryonic cells and induced pluripotent stem cells were generated to be used in the experiment. By exposing the pluripotent stem cells to BMP4 in vitro, results showed that these cells would 'upregulate' the chromaffin cell - specific marker PMNT (an enzyme that synthesizes adrenaline). Furthermore when the cells from human embryos were implanted into avian embryos, there was a visible potential for the human cells to differentiate into cells that expressed the chromaffin cell markers{{#pmid:5768882|PMID5768882}}.<br /> <br /> <br /> ====Multipotent Peripheral Glial Cells Generate Neuroendocrine Cells of the Adrenal Medulla====<br /> <br /> Similar to the first study, this one also focuses on the chromaffin cells and their relationship to the adrenal medulla. Chromaffin cells often represent the main endocrine component that is believed to differentiate from neural crest cells{{#pmid:28684471|PMID28684471}}. The study focuses specifically on the idea that previous research has suggested that nerve - associated schwann cell precursor is a progenitor of chromaffin cells. What the findings suggested was that peripheral nerves provided migration routes for the progenitors. This is backed up by the results, a high concentration of chromaffin cells can be found being derived from the nerve, as nerve ablated mice in the experiment showed a large difference of 78% less cells compared to the control. Other than this, the study also brought to light the proliferative potential of the cells from nerves, with different other cell types being discovered as well (including cells such as parasympathetic{{#pmid:24925912|PMID24925912}} and melanocytes {{#pmid:19837037 |PMID19837037}}). The findings would provide useful information into further understanding the adrenal gland and its embryonic origins (as there is still much to learn regarding the formation of the adrenal medulla) but also pathological diseases such as neuroblastoma and pheochromatocytoma which are most common in the adrenal glandular region {{#pmid:23106811|PMID23106811}}.<br /> <br /> ===Glossary===<br /> ----<br /> ===Reference list===</div>

Z5091101 https://embryology.med.unsw.edu.au/embryology/index.php?title=2018_Group_Project_1&diff=358287 2018 Group Project 1 2018-10-16T00:38:19Z

<p>Z5091101: /* History */</p> <hr /> <div>=The Contribution of Neural Crest Cells to the Adrenal Medulla=<br /> ----<br /> {{2018ANAT2341ProjectHeader}}<br /> <br /> <br /> ===Introduction===<br /> <br /> ----<br /> <br /> The neural crest of an embryo differentiates and migrates to form various components of the body. This transient population of pluripotent stem-cells give rise to many complex and different structures across the adult by chemical signalling. One of these tissues is the medulla of the adrenal gland which is involved in the production of epinephrine and norepinephrine. This project will comprehensively outline the history of neural crest research, the embryonic developmental time course, tissue and organ structure, molecular mechanisms, abnormalities, animal models and current research.<br /> <br /> ===History===<br /> ----<br /> '''Describing the neural crest'''<br /> [[File:Wilhelm_His_History_Wilhelm.jpeg|left|230px|thumb|Wilhelm His]]<br /> The "neural crest" is a structure in the embryo and is the junction between the neural and epidermal ectoderm. It is exclusive to vertebrates and forms a range of structures{{#pmid:22230617|PMID22230617}}. The neural crest contributes a large number of cells of varying structure and function that directly or indirectly contribute to the development of tissues and organs within the body {{#pmid:19179766|PMID19179766}}. In 1868, the neural crest cells were first identified in a chick embryo as a collection of cells known as "Zwischenstrang" by Professor Wilhelm His {{#pmid:22820859|PMID22820859}}. Wilhelm His was among the first to provide an explanation for the mechanics governing the developing embryo as well as the physiology and the organs that the differing germinal regions would eventually give rise to. In 1878, the term neural ridge was used to describe this collection of cells but the term neural crest was later coined by Arthur Milnes Marshall in 1879 in a paper he worked on disseminating the knowledge from his research on the development of cranial nerves in chicken embryos. {{#pmid:19179766|PMID19179766}}.<br /> [[File:NC Location.jpg|right|450px|thumb|The neural crest]]<br /> <br /> '''1890s-1950s'''<br /> The neural crest is the point of origin for spinal/cranial ganglia and neurons. This theory received little criticism and was not contested much by other researchers prior to the 1890s. This is owing to the fact that the neural crest is quite closely related to the neural tube and thus this relationship makes sense. This discovery was made by His and Marshall, however, they found this out independently of one another.In the 1890s, Julia Platt, claimed that odontoblasts as well as the cartilages forming the facial and pharyngeal arch skeletons came from the ectoderm. This created much debate and was contested by many{{#pmid:22820859|PMID22820859}}. <br /> <br /> This is because this theory completely contradicted the germ-layer theory, whereby skeletal tissues originate at the mesoderm and not the ectoderm. The controversies this finding created brought about a slowing down of research, as demonstrated by a gap of almost 40 years between the theory that skeletal tissues originating from the neural crest. Today, it is known that the neural crest does indeed play a role in the development of the skeleton in vertebrates, particularly, the cranial neural crest. Although these studies were occurring, the focus was still primarily on researching pigment cells and ganglia of the spine up until the 1950s, when Sven Hörstadius' major work on the neural crest was published, titled "The Neural Crest: Its properties and derivatives in the light of experimental research". This work focused on experimental data tracing the development of the cartilaginous skeleton derived from the neural crest {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1960s - 1970s'''<br /> In the 1960s, the migration patterns of neural crest cells were studied in avian embryos (birds). This was a shift from studying the embryos of amphibians. This was inspired by studies conducted in the 1960s on neural crest cells migrating from the brain and spinal cord, known as trunk and cranial neural crest cells {{#pmid:19179766|PMID19179766}}. The cranial neural crest eventually becomes the bones, cartilage and connective tissues forming the foundation of the face, ears and teeth. The trunk neural crest cells can either become melanocytes or can migrate into sclerotomes which are later contributors to the cartilage of the spine and the dorsal root ganglia {{#pmid:22820859|PMID22820859}}. The cells in the trunk neural crest that migrate vertically become the sympathetic ganglia, the nerves proximal to the aorta and the adrenal medulla <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. In the 1970s many detailed maps signifying the pathways of many of the neural crest cells appeared as well as an understanding that the environment in which the neural crest cells are found plays a major role in their final development as well as the occurrences of abnormalities in the fetus {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1980s - 21st century'''<br /> [[File:Regions_of_NC_Cells.jpg|left|Neural crest regions|thumb|500px]]<br /> From the 1980s-1990s, the causative agent of organ transformation from one to another (homeotic patterning), as well as the Hox genes which regulate the axis of most symmetrical animal embryos were founded and studied. The neural crest, which previously was divided into the cranial and trunk regions, was now further divided into the vagal and sacral neural crest, the cardiac neural crest and the cephalic neural crest {{#pmid:19179766|PMID19179766}}. The vagal & sacral neural crest gives rise to the parasympathetic ganglia found in the gut. Without these ganglia, peristalsis, is not possible <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. The cardiac neural crest contributes to the valves, septa and major blood vessels of the heart, as well as connective tissues and cartilage{{#pmid:19179766|PMID19179766}}. This is important for the structure of the heart as well as its overall function, enabling it to move blood around the body efficiently as well as keep pulmonary and aortic circulation separated <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> <br /> <br /> Today, knowledge of the neural crest cells, their migration patterns, modes of differentiation, derivatives and apoptosis (cell death) are being studied extensively. This is being done on a comparative basis between different organisms, to add further evidence for evolution {{#pmid:19179766|PMID19179766}}. The neural crest is definitely forging a "crest" between the fields of developmental and evolutionary biology, as it is a structure '''shared exclusively by all vertebrates'''. Invertebrates do not derive their specialised cells from the neural crest as they do not have one, rather, they derive these from the endomesoderm {{#pmid:22230617|PMID22230617}}.<br /> <br /> '''Future directions'''<br /> <br /> Since its discovery by His, the neural crest field has made great progress, from studies performed on the structure, to analysis of the molecules and whether certain aspects of the neural crest are specific to a single species of organism, or to all vertebrates collectively. Future work on the cranial neural crest needs to be done as well as identifying and categorising the networks responsible for the proliferation and death of cells, as well as how the cells move and migrate, as well as the gene regulatory networks (GRNs) that regulate the synthesis of proteins. Advances in technology will undeniably lead us to more answers on the subject {{#pmid:22230617|PMID22230617}}.<br /> <br /> ===Developmental time course===<br /> ---- <br /> <br /> [[File:Adrenal_Medulla_Developmental_Timeline.jpg|right|thumb|500px]]<br /> <br /> The adrenal gland has two distinct sections, the cortex and the medulla, both with different embryonic origins. The cortex accounts for 90% of the adrenal glands and arises from intermediate mesoderm. The medulla only accounts for 10% of the adult adrenal glands, however it has neural crest embryonic origin. The medulla consists of chromaffinoblast cells which are migrant neuroblast cells from the neural crest, therefore the adrenal medulla is a component of the sympathetic nervous system.{{#pmid:21175739|PMID21175739}} Neural crest cells replicate in week 7 and begin to differentiate in week 8, the cells then migrate to the developing adrenal gland in week 9 of development.{{#pmid:25255746|PMID25255746}}{{#pmid:18279781|PMID18279781}} The neural crest cells infiltrate the cortex and the chromaffin cells are scattered islands in the cortex.{{#pmid:23354096|PMID23354096}} Throughout development the cells will become more compact in the centre of the gland, during this period of development the adrenal gland is growing rapidly. The gland is abnormally large until the second trimester and the medulla is much thicker prenatally.{{#pmid:18279781|PMID18279781}}{{#pmid:21175739|PMID21175739}}<br /> <br /> <br /> ===Embryonic origins===<br /> ----<br /> [[File:Trunk_NCC_migration.jpg|left|450px|thumb|Trunk NCC migration]]<br /> The adrenal gland is made up of the adrenal cortex and adrenal medulla, which both have different embryonic origins. The adrenal medulla arises from the neural crest tissue, found near the level of the coeliac plexus & sympathetic ganglion at somites 18-24 {{#pmid:16124976|PMID16124976}}. Specifically, this neural crest tissue comes from the trunk neural crest cells (see above figure to determine the approximate location in an embryo) <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> The trunk neural crest coordinates the development of the endocrine system, secretory cells, the peripheral nervous system and, to some degree, skeletal development, as well as innervation of the intestine {{#pmid: 28287247|PMID 28287247}}. The trunk neural cells arise caudally, undergo an epithelial to mesenchymal transition and follow three migratory pathways {{#pmid:20399766|PMID20399766}}.<br /> [[File:Differentiation_of_NCC.jpg|left|580px|thumb|Differentiation of chromaffin cells]]<br /> - A dorsolateral pathway (between ectoderm and somites), these become melanocytes, travel up to the point of the dermis and become a major part of the hair follicles and skin <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> - A ventrolateral pathway (through the somites)<br /> - A ventromedial pathway (between neural tube and posterior schlerotome){{#pmid:20399766|PMID20399766}}.<br /> <br /> Migration of neural crest cells from the sympathetic ganglion is what leads to the development of the adrenal medulla. In week 8 of development, immature cells called neuroblasts migrate through to the inner portion of the medulla, where they become the adrenal medulla {{#pmid:19683477|PMID19683477}}. Chromaffin cells are neuroendocrine cells and are found in the sympathetic ganglia and make up the majority of the adrenal medulla{{#pmid:19683477|PMID19683477}}. They synthesise and release a range of hormones in the body and arise from the temporary neural crest. The term chromaffin was inspired by the staining capacity of these cells when they came into contact with chrome salts. They make, store, export and use catecholamines, responsible for making noradrenaline and originate at the caudal region of somites 18-24 of the neural crest, also known as the adrenomedullary region {{#pmid:19683477|PMID19683477}}.<br /> <br /> For cells to leave the neural crest and begin their migration, certain conditions need to be met, that is, the cells need to be loosely connected, their tight junctions becoming relaxed, initiated by "Slug protein" and a loss of N-Cadherin which also leads to the loosening of these junctions. The surrounding matrix as well as chemotactic and stem cell factors of the neural tube are then what dictates how the neural crest cells move, some proteins stopping their migration to that area and others encouraging the movement <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. After splitting apart, the first neural crest cells move ventrally and pass into the spaces between the somites and then, through the anterior portions of each segment until they arrive at the para-aortic sites, where they become the cells of the sympathetic ganglia and the adrenal medulla {{#pmid:19683477|PMID19683477}}. BMP-4 (bone morphogenetic protein 4) then acts on these neural crest cells, preventing them from becoming cells that have a neural function and causing them to become chromaffin cells at the adrenal medulla. Glucocorticoids then play a role in maintenance of chromaffin cells in postnatal life, this was only found recently, as previously it was thought that glucocorticoids were responsible entirely for the differentiation of neural crest cells into chromaffin, or adrenomedullary cells {{#pmid:23220335|PMID23220335}}.<br /> <br /> ===Anatomy and Functions===<br /> <br /> ----<br /> <br /> ====Anatomy and Histology====<br /> <br /> The adrenal medulla makes up the inner section of the adrenal glands, and is surrounded by the cortex, and a connective tissue capsule. It lies in the centre of the gland and it rarely measures no more than 2mm in thickness {{#pmid:21107679|PMID21107679}}. The cells of the adrenal medulla are derived from the neural crest as opposed to the mesodermal origins of the cortex. The adrenal medulla contains secretory cells called chromaffin cells due to the agents they produce when oxidised, such as chromate {{#pmid:11215683|PMID11215683}}. These cells secrete epinephrine, norepinephrine, chromogranin and neuropeptides in response to various substances such as acetylcholine <ref name="PMID11215683"/>. [[File:ADRENAL MEDULLA .jpg|600px|thumb|right|Adrenal Medulla Histology]]<br /> <br /> There are many types of highly differentiated cells in the adult adrenal medulla: <br /> - Epinephrine cells (90% of all chromaffin cells) {{#pmid:24715564|PMID24715564}}<br /> - Norepinephrine cells (10% of all chromaffin cells) <ref name="PMID24715564"/><br /> - Small granule-containing cells (SGCs) <ref name="PMID11215683"/><br /> <br /> These cells also synthesise, store and secrete catecholamines through controlled and regulated pathways <ref name="PMID24715564"/>, such as various peptides like substance P and neurotensin.These cells have unique neuroendocrine characteristics as a result of their neural-crest origin. They receive preganglionic innervation by thoracic splanchnic nerves, and could almost be considered a specialised sympathetic ganglion. With postganglgionic bodies, cells of the medulla are densely clustered around their vasculature for the secretion of hormones into the bloodstream to moderate the concentration of epinephrine and norepinephrine. The adrenal medulla also contains presynaptic sympathetic ganglion cells <ref name="PMID11215683"/>. The small granule-containing cells are usually found in clusters whereas, the ganglion cells are found either individually or in clusters, usually dispersed among the chromaffin cells or among the nerve fibres {{#pmid:18021328|PMID18021328}}. During embryonic development (around weeks 9-12), in contrast to the developing adrenal cortex, the medulla does not show evidence of an organised structure other than a small cluster of cells scattered throughout its cortex {{#pmid:30247985|PMID30247985}}. <br /> <br /> <br /> <br /> ====Related Anatomy====<br /> <br /> The tissue and organ structure of the adrenal medulla should be understood with regard to its specialised function within the sympathetic nervous system. <br /> <br /> The medullary region of the adrenal glands is tasked with the endocrine secretions of adrenaline and nor-adrenaline in response to environmental stressors that are signalled for by the sympathetic nervous system. That is, the secretion of fight-or-flight response hormones in order to restrict vasculature to the trunk and increase vascular activity in the peripheral musculature.<br /> <br /> The adrenal glands are supplied by several branches of the great vessels in the abdominal cavity. The secreted catecholamines in the medulla are directly able to pass to the blood stream this way.<br /> <br /> These adrenal glands and their contents are retroperitoneal in the adult and varied in shape, with the left often being semilunar and right being pyramidal. Nervous supply of the adrenal glands is achieved by contributions from the splanchnic nerves of the celiac plexus. {{#pmid:11215683|PMID11215683}} <br /> <br /> [[File:Dd.jpg|400px|thumb|right|Adult Adrenal Glands in situ]] <br /> ----<br /> ====Role of the Adrenal Medulla====<br /> <br /> Understanding the biochemistry of catecholamines is necessary to see how the adrenal medulla is designed in the stages of embryology and how it is suited for life in the neonate and adult. <br /> <br /> The epinephrine and norepinephrine in the neonate and adult work by primarily changing the osmoregulatory state of vasculature in organs. With the exclusion of their neuromodulatory and neurotransmitter functions, epinephrine and norepinephrine are mainly tasked with the control of sympathetic and parasympathetic supplies. <br /> <br /> Norepinephrine is a constrictor of peripheral vasculature by antagonising the action of surface receptors expressed on the endothelium of blood vessels, specifically Alpha-1 and Alpha-2 receptors, such that vascular resistance increases. <br /> <br /> Epinephrine is both a vasoconstrictor and vasodilator, depending on what receptors it attaches to. As a non-selective adrenergic agonist, it acts on Alpha-1, Alpha-2, Beta-1, Beta-2 and Beta-3 receptors that are found throughout the body's tissues, yielding many different physiological responses. {{#pmid:19396395|PMID19396395}}<br /> <br /> '''Adult Function'''<br /> <br /> While the adrenal cortex releases glucocorticoids in response to long term stress, the adrenal medulla releases its hormones in response to short-term, acute stress. The adrenal medulla contains the neuroendocrine chromaffin cells which are responsible for secreting adrenaline and noradrenaline. The function of these hormones is primarily to maintain the body’s homeostasis, especially of the internal organs, and to properly activate the autonomic stress response, more commonly known as the ‘fight or flight’ response {{#pmid:30237243|PMID30237243}}. Thus the function of the medulla includes signalling the liver and skeletal muscles to convert glycogen into glucose for increased energy. This results in increased blood glucose levels. These hormones also increase the heart rate, pulse and blood pressure in preparation for the fight or flight response. In addition to this, these hormones dilate the lung airways and prompt vasodilation to further increase oxygenation of important organs such as the lung, brain and heart. Vasoconstriction of blood vessels is also prompted to other less essential organs such as the bladder and the digestive system.<br /> <br /> Other effects also include pupil dilation, dry mouth and a loss in peripheral vision <ref name="PMID18021328"/>. Paramount to the correct response of chromaffin cells is the synaptic connection of the preganglionic cells which originate from the central nervous system and project axons into the adrenal medulla. While this is a very important relationship, the mechanisms of this remains unknown <ref name="PMID30237243"/>. In addition to the release of catecholamines, cells in the medulla also release peptides through the process of exocytosis from chromaffin granules, to help regulate blood pressure and regulation throughout the body. These peptides also regulate the release of adrenaline and noradrenaline, blood vessel contraction and the immune response <ref name="PMID18021328"/>. <br /> <br /> '''Embryonic function'''<br /> <br /> The current knowledge about the development of the adrenal gland is limited, with nearly all models being from animals, and very limited functional data available from human fetal adrenals <ref name="PMID30247985"/>. Thus for these reasons, there is scarce information available on the embryonic adrenal medullary functions. Nevertheless, there is accumulating evidence that the catecholamines in the fetal adrenal medulla plays an important role in the time of delivery by controlling thermogenesis and heart regulation {{#pmid:6998630|PMID6998630}}. <br /> <br /> The hormones released by the medulla during birth also play a key role for the newborn’s adaptation to extrauterine life. Despite the immaturity of the adrenal medulla at birth, it is known that respiratory, metabolic and cardiovascular changes during delivery are dependent on the adrenomedullary hormones {{#pmid:3280659|PMID3280659}}. Experimental data from human and animal fetal research shows that the fetal sympathoadrenal system, consisting of the adrenal medulla, sympathetic neurons and chromaffin tissue work together to maintain fetal homeostasis {{#pmid:6346884|PMID6346884}}. The adrenal medulla thus appears to provide vital physiological functions for fetal and neonatal survival, especially during birth. <br /> <br /> <br /> ----<br /> <br /> ===Molecular mechanisms/factors/genes===<br /> ----<br /> <br /> ====Genes and Transcription Factors Involved with the Adrenal Medulla's Development====<br /> <br /> The 'story' of the Adrenal Medulla's neural crest tissue begins at the process of neurulation, the formation of the neural tube from the folding neural plate, which is comprised of developing ectoderm which is opposite to the primitive streak. It is here that several key chemical players are at work. The classic interpretation of Sonic Hedgehog (Shh) and Wnt signalling pathways as the only mediators here, has been shown to be incorrect. Research has uncovered other signallers such as: <br /> <br /> *Bone-Morphogenic-Protein-4 (BMP4) for the regional expression of nervous system distinctions in the growing neural plate. This maintains two important embryonic trancription factors known as Paired-Box (PAX) Genes 3 and 7 which can allow for expression of neural crest markers HNK-1, SRY-Box (SOX) 8, 9 and 10 as the neural tube closes and the neural crest delaminates from the folding. {{#pmid:16688176|PMID16688176}} <br /> <br /> *Slug via Wnt signalling, this allows for the loosening of gap junctions in the extracellular matrix surrounding the newly-formed neural tube and trunk of the embryo. This extracellular matrix has chemo-attractant molecules<br /> <br /> [[File:Catecholamine_Synthesis.jpg|400px|thumb|right|Biochemical Cascade of Catecholamine Synthesis]]<br /> <br /> The importance of Somitogenesis and Neural Crest come to a head when neural crest cells must migrate anteriorly past somites 18 to 24 <br /> <br /> Members of the SOX gene family have multiple key contributors to Neural Crest in the Adrenal Medulla.<br /> <br /> <br /> Mouse models have demonstrated that SOX-10 knock-outs (mice whose DNA has been engineered to not express SOX-10) do not have an adrenal medulla. There has also been suggestion that SOX-8,9 and 10 are all strongly related to the migratory patterning of neural crest cells to the developing adrenal glands. {{#pmid:18272785|PMID18272785}}<br /> <br /> The TH gene (for Tyrosine Hydroxylase) encodes the aforementioned enzyme in the adrenal medulla and central nervous system. Tyrosine Hydroxylase is crucial in biochemical pathways and cascades for the synthesis of catecholamines and other CNS neurotransmitters. The conversion from L-Tyrosine to L-DOPA is dependent upon the catalytic action of Tyrosine Hydroxylase. From there, L-DOPA can make Dopamine and eventually Epinephrine and Norepinephrine as well. {{#pmid:19396395|PMID19396395}}<br /> <br /> ===Abnormalities/abnormal development===<br /> ----<br /> <br /> Abnormalities of the Adrenal Medulla are much less common than its mesoderm-derived shell of the Adrenal Gland. Three of the most notorious abnormalities of the Adrenal Medulla include:<br /> <br /> * Pheochromocytomas<br /> * Ganglioneuromas<br /> * Neuroblastomas<br /> <br /> <br /> Pheochromocytomas (PCCs) are variable neoplasias of the adrenal medulla's chromaffin cells. There are many classifications of PCCs, with autosomal-dominant germ-line mutations and heredities being one of the main causes. Familial phaeochromocytoma-paraganglioma (PGL) syndromes exist, with PGL1 having mutations of the SDHD gene, PGL3 being mutated of the SDHC gene and PGL4 having mutation of the SDHB gene. These phenotypically present as extra-adrenal chromaffin bodies, malformation of the adrenal glands themselves, absence of chromaffin bodies and fluctuations in circulating catecholamines. {{#pmid:18021328|PMID18021328}}<br /> <br /> Ganglioneuromas (GNs) are classically-benign growths that are very rare and arise from neural crest tissue. They are not circumscribed to the adrenal medulla, but also are found in the sympathetic chain and trunk ganglia. As a result of their scarcity, not much is known about them other than a few aberrant genes and generic clinical presentations. ERBB3, the receptor tyrosine kinas is understood to be important in the development of GNs, as well as an extremely high prevalence of up-regulated GATA3. A key thing to note is also the '''lack''' of N-MYC expression in GNs, which is quite prominent in neuroblastomas and other neoplasias. {{#pmid:29085827|PMID29085827}} {{#pmid:23715162|PMID23715162}} <br /> <br /> Neuroblastomas (NBs) are a more aggressive form of cancer, derived from neuroblasts - the precursor cells to neurons. A rather common pediatric cancer, they are often in children who are in risk factor groups such as those with aforementioned familial cancer syndromes, neurofibromatosis-1. These tumours often present with extremely variable catecholamine concentrations, which has implications for blood pressure, heart contractility and much more. Urinary excretion of norepinephrine, homovanillic acid (HVA) and vanilmandelic acid (VMA) can be used to help diagnose a suspected lesion of the adrenal gland, as these chemicals are associated with altered chemical cascades that are suspicious of neuroblastic change. {{#pmid:16372223|PMID16372223}}<br /> <br /> <br /> Apart from these abnormalities, there are other pathologies that may be connected to the adrenal medulla. One such example is a pathology of the Organ of Zuckerkandl. Also known as the para-aortic body, the Organ of Zuckerkandl is a primarily-gestational organ comprised of chromaffin cells and serves a similar purpose to the adrenal medulla in neonatal life.<br /> <br /> ===Animal models===<br /> ----<br /> Animal models are an integral part of research in embryology. In particular due to the moral concerns regarding the use of humans in scientific research. As a result different animals are used as substitutes to simulate the same environments and hope to achieve results that would also be able to represent humans as well. Prenatal adrenal gland development has been described in a number of scientific reports dating from the 1900s to studies in more recent years. These involved a variety of animal models such as ox, sheep, swine and most commonly mice. <br /> <br /> ====Chromaffin cells====<br /> There has been extensive research conducted into the adrenal chromaffin cells and their embryological developments. As explained above nueral crest cells are pluripotent meaning they are able to differentiate into multiple different cells{{#pmid:19377845|PMID19377845}}. The neural crest cells give rise to chromaffin cells of the adrenal medulla.<br /> <br /> =====Rat Models=====<br /> [[File:Adrenal gland.png|300px|thumb|right|3D images showing TH - positive cells accumulating at the cranial and audal ends of the adrenal gland. A. A observation of adrenal gland and surrounding structures (at 17 days of gestation). B. Enhanced image to further focus on the dark TH - positive cells. C. Image with the other structures removed.]]<br /> Previous research has reported that nueral crest cells differentiate into chromaffin cells around 19 days of gestation before forming the adrenal medulla{{#pmid:28684471|PMID2868441}}. Past research had also suggested that neural crest derived adrenal gland cells migrate using the sympathetic ganglia to the adrenal gland or preaortic ganglion, following different pathways, to reach their specific destination. However the results have shown that the pathways used to reach its destinations overlapped. This would suggest that there is a possibility of the cells using the same pathway to move from the beginning production to the destination that is the adrenal medulla (for chromaffin cells) and the preaortic ganglion (other cells involved in the sympathetic system). <br /> <br /> One particular study done by M.Yamato in 2004, along with his fellow scientists attempted to study the migration of neural crest cells in Wistar rats. In order to observe the formation adrenal medulla from the neural crest cells during the embryonic period, Yamato used anti - tyrosine hydroxylase (TH) antiserum injected into the rat embryos between 13-17 days of gestation. The anti - TH antiserum stain allows the scientists to visualize the neural crest cells under a light microscope. Later three dimensional images were created. From the images observed between 13 to 15 days of gestation, the TH - positive cells can be seen to move from the dorsal to the adrenal primordium{{#pmid:15240937|PMID15240937}}. After 16 days it was observed that a capsule had formed in some parts and TH - positive cells had penetrated the adrenal gland{{#pmid:15240937|PMID15240937}}. At seventeen days, TH - positive cells can be seen collecting at the medial part of the adrenal gland. The reconstructed images also shows that at the later stages during the 16-17 days of gestation, the accumulation of TH - positive cells grow and in combination with cell division leads to the formation of the adrenal medulla.<br /> <br /> =====Chicken models=====<br /> Chicken and rat models are often the most commonly used models when dealing with neural crest cells. In this particular review, collates multiple researchers results and presents evidence to discuss previous information suggesting that sympathetic neurons and chromaffin cells do not share a common progenitor{{#pmid:3693940|PMID3693940}}. The relevant study involved the use of cell cultures, Sympathoadrneal (SA) progenitor cells from embryonic(from chick embryos) and eary developmental stages were able to be procured. From these cultures it was easy to identify that glucocorticoids were crucial in the differentiation of SA cells into their derivatives, sympathetic neurons and chromaffin cells.<br /> <br /> [[File:Expression of BMP protein 4 .jpg|300px|thumb|right|Expression of BMP - 4 in the adrenal cortex at developmental stages. Shows the movement of the chromaffin progenitors moving from each stage of development. A-D: collection of progenitors outside E-H: cells have begun to penetrate the adrenal cortical region I-L: chromaffin cells have completely intergrated intergreted within the gland sg: sympathetic ganglia ac:adrenal cortical region ag: adrenal gland da: dorsal aortic region]]<br /> <br /> Another study conducted deals with the role of the bone morphogenetic protein(BMP-4) and its importance in the development of the adrenal medullary cells, chromaffin cells{{#pmid:18945349|PMID18945349}}. Previous research had shown that BMP - 4 a growth factor is plays an important role in the regulation of chromaffin cell production{{#pmid:10679774|PMID10679774}}. The researchers incubated chick embryos for 3 - 9 embryonic days and dissected them to be used for tissue cultures. Embryonic day 8 chick embryos had BMP - 4 overexpressing cells implanted in the sympathetic ganglia area, as well as other neurons which contained chromaffin like cells. What was observed was an increase in size and numbers of 'chromaffin' granules{{#pmid:18945349|PMID18945349}}. As a result it was concluded that although BMP - 4 promotes certain chromaffin traits, it does not have the capability to convert sympathetic neurons into a chromaffin type cell.<br /> <br /> ===Current research (labs)===<br /> ----<br /> <br /> ==== Generation of Adrenal Chromaffin-like Cells from Human Pluripotent Stem Cells====<br /> <br /> As explained above the adrenal medulla plays an important part in the autonomic system of an adult human. The chromaffin cells, in particular, are important neural crest derived cell that is closely related to the adrenal medulla. Previous findings have focused specifically on the mechanisms controlling the NCC migration and how these cells go on to form the different derivatives in their particular destinations in the embryo. For example, as previously explained studies have shown that chromaffin cells have been observed to move to the adrenal gland to form the medulla of the adrenal gland. This report goes through a recent study that involves the adrenal medullary cells, in particular chromaffin cells, and their potential to be used to model certain pathological diseases related to these cells. This is part of a study that also involves neural crest cells and their ability to differentiate into multiple different types of cells<ref>Lumb, R., & Schwarz, Q. (2015). Sympathoadrenal neural crest cells: The known, unknown and forgotten?. Development, Growth & Differentiation, 57(2), 146-157. doi: 10.1111/dgd.12189</ref>. Neural crest cells and SAPs from human embryonic cells and induced pluripotent stem cells were generated to be used in the experiment. By exposing the pluripotent stem cells to BMP4 in vitro, results showed that these cells would 'upregulate' the chromaffin cell - specific marker PMNT (an enzyme that synthesizes adrenaline). Furthermore when the cells from human embryos were implanted into avian embryos, there was a visible potential for the human cells to differentiate into cells that expressed the chromaffin cell markers{{#pmid:5768882|PMID5768882}}.<br /> <br /> <br /> ====Multipotent Peripheral Glial Cells Generate Neuroendocrine Cells of the Adrenal Medulla====<br /> <br /> Similar to the first study, this one also focuses on the chromaffin cells and their relationship to the adrenal medulla. Chromaffin cells often represent the main endocrine component that is believed to differentiate from neural crest cells{{#pmid:28684471|PMID28684471}}. The study focuses specifically on the idea that previous research has suggested that nerve - associated schwann cell precursor is a progenitor of chromaffin cells. What the findings suggested was that peripheral nerves provided migration routes for the progenitors. This is backed up by the results, a high concentration of chromaffin cells can be found being derived from the nerve, as nerve ablated mice in the experiment showed a large difference of 78% less cells compared to the control. Other than this, the study also brought to light the proliferative potential of the cells from nerves, with different other cell types being discovered as well (including cells such as parasympathetic{{#pmid:24925912|PMID24925912}} and melanocytes {{#pmid:19837037 |PMID19837037}}). The findings would provide useful information into further understanding the adrenal gland and its embryonic origins (as there is still much to learn regarding the formation of the adrenal medulla) but also pathological diseases such as neuroblastoma and pheochromatocytoma which are most common in the adrenal glandular region {{#pmid:23106811|PMID23106811}}.<br /> <br /> ===Glossary===<br /> ----<br /> ===Reference list===</div>

Z5091101 https://embryology.med.unsw.edu.au/embryology/index.php?title=File:Differentiation_of_NCC.jpg&diff=358263 File:Differentiation of NCC.jpg 2018-10-16T00:18:59Z

<p>Z5091101: </p> <hr /> <div>The neural crest cells become chromaffin precursor cells under exposure to BMP-4, and their growth and postnatal health is maintained by the secretion of glucocorticoids.<br /> <br /> <br /> This image was inspired by the following figure on the link below, however the information was altered slightly, due to recent studies showing that glucocorticoids do not initially cause neural crest cells to become chromaffin cells, but rather BMP-4 protein{{#pmid:23220335|PMID23220335}}:<br /> https://www.ncbi.nlm.nih.gov/books/NBK10065/figure/A3132/?report=objectonly <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>.<br /> <br /> <br /> <br /> NCC - Neural crest cells</div>

Z5091101 https://embryology.med.unsw.edu.au/embryology/index.php?title=2018_Group_Project_1&diff=356853 2018 Group Project 1 2018-10-12T02:00:38Z

<p>Z5091101: /* History */</p> <hr /> <div>=The Contribution of Neural Crest Cells to the Adrenal Medulla=<br /> ----<br /> {{2018ANAT2341ProjectHeader}}<br /> <br /> <br /> ===Introduction===<br /> [[User:Z5014972|Z5014972]] ([[User talk:Z5014972|talk]]) 12:47, 14 August 2018 (AEST)z5014972 <br /> good review article https://link.springer.com/article/10.1007%2Fs12022-009-9070-6<br /> ----<br /> <br /> <br /> The neural crest of an embryo differentiates and migrates to form various components of the body. One of these tissues is the medulla of the adrenal gland which is involved in the production of adrenalin and noradrenalin. This project will comprehensively outline the history of neural crest research, the embryonic developmental time course, tissue and organ structure, molecular mechanisms, abnormalities, animal models and current research.<br /> <br /> ===History===<br /> ----<br /> '''Describing the neural crest'''<br /> [[File:Wilhelm_His_History_Wilhelm.jpeg|left|230px|thumb|Wilhelm His]]<br /> The "neural crest" is a structure in the embryo and is the junction between the neural and epidermal ectoderm. It is exclusive to vertebrates and forms a range of structures{{#pmid:22230617|PMID22230617}}. The neural crest contributes a large number of cells of varying structure and function that directly or indirectly contribute to the development of tissues and organs within the body {{#pmid:19179766|PMID19179766}}. In 1868, the neural crest cells were first identified in a chick embryo as a collection of cells known as "Zwischenstrang" by Professor Wilhelm His {{#pmid:22820859|PMID22820859}}. Wilhelm His was among the first to provide an explanation for the mechanics governing the developing embryo as well as the physiology and the organs that the differing germinal regions would eventually give rise to. In 1878, the term neural ridge was used to describe this collection of cells but the term neural crest was later coined by Arthur Milnes Marshall in 1879 in a paper he worked on disseminating the knowledge from his research on the development of cranial nerves in chicken embryos. {{#pmid:19179766|PMID19179766}}.<br /> [[File:NC Location.jpg|left|450px|thumb|The neural crest]]<br /> <br /> '''1890s-1950s'''<br /> The neural crest is the point of origin for spinal/cranial ganglia and neurons. This theory received little criticism and was not contested much by other researchers prior to the 1890s. This is owing to the fact that the neural crest is quite closely related to the neural tube and thus this relationship makes sense. This discovery was made by His and Marshall, however, they found this out independently of one another.In the 1890s, Julia Platt, claimed that odontoblasts as well as the cartilages forming the facial and pharyngeal arch skeletons came from the ectoderm. This created much debate and was contested by many{{#pmid:22820859|PMID22820859}}. <br /> <br /> This is because this theory completely contradicted the germ-layer theory, whereby skeletal tissues originate at the mesoderm and not the ectoderm. The controversies this finding created brought about a slowing down of research, as demonstrated by a gap of almost 40 years between the theory that skeletal tissues originating from the neural crest. Today, it is known that the neural crest does indeed play a role in the development of the skeleton in vertebrates, particularly, the cranial neural crest. Although these studies were occurring, the focus was still primarily on researching pigment cells and ganglia of the spine up until the 1950s, when Sven Hörstadius' major work on the neural crest was published, titled "The Neural Crest: Its properties and derivatives in the light of experimental research". This work focused on experimental data tracing the development of the cartilaginous skeleton derived from the neural crest {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1960s - 1970s'''<br /> In the 1960s, the migration patterns of neural crest cells were studied in avian embryos (birds). This was a shift from studying the embryos of amphibians. This was inspired by studies conducted in the 1960s on neural crest cells migrating from the brain and spinal cord, known as trunk and cranial neural crest cells {{#pmid:19179766|PMID19179766}}. The cranial neural crest eventually becomes the bones, cartilage and connective tissues forming the foundation of the face, ears and teeth. The trunk neural crest cells can either become melanocytes or can migrate into sclerotomes which are later contributors to the cartilage of the spine and the dorsal root ganglia {{#pmid:22820859|PMID22820859}}. The cells in the trunk neural crest that migrate vertically become the sympathetic ganglia, the nerves proximal to the aorta and the adrenal medulla <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. In the 1970s many detailed maps signifying the pathways of many of the neural crest cells appeared as well as an understanding that the environment in which the neural crest cells are found plays a major role in their final development as well as the occurrences of abnormalities in the fetus {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1980s - 21st century'''<br /> [[File:Regions_of_NC_Cells.jpg|left|Neural crest regions|thumb]]<br /> From the 1980s-1990s, the causative agent of organ transformation from one to another (homeotic patterning), as well as the Hox genes which regulate the axis of most symmetrical animal embryos were founded and studied. The neural crest, which previously was divided into the cranial and trunk regions, was now further divided into the vagal and sacral neural crest, the cardiac neural crest and the cephalic neural crest {{#pmid:19179766|PMID19179766}}. The vagal & sacral neural crest gives rise to the parasympathetic ganglia found in the gut. Without these ganglia, peristalsis, is not possible <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. The cardiac neural crest contributes to the valves, septa and major blood vessels of the heart, as well as connective tissues and cartilage{{#pmid:19179766|PMID19179766}}. This is important for the structure of the heart as well as its overall function, enabling it to move blood around the body efficiently as well as keep pulmonary and aortic circulation separated <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> <br /> <br /> Today, knowledge of the neural crest cells, their migration patterns, modes of differentiation, derivatives and apoptosis (cell death) are being studied extensively. This is being done on a comparative basis between different organisms, to add further evidence for evolution {{#pmid:19179766|PMID19179766}}. The neural crest is definitely forging a "crest" between the fields of developmental and evolutionary biology, as it is a structure '''shared exclusively by all vertebrates'''. Invertebrates do not derive their specialised cells from the neural crest as they do not have one, rather, they derive these from the endomesoderm {{#pmid:22230617|PMID22230617}}.<br /> <br /> '''Future directions'''<br /> <br /> Since its discovery by His, the neural crest field has made great progress, from studies performed on the structure, to analysis of the molecules and whether certain aspects of the neural crest are specific to a single species of organism, or to all vertebrates collectively. Future work on the cranial neural crest needs to be done as well as identifying and categorising the networks responsible for the proliferation and death of cells, as well as how the cells move and migrate, as well as the gene regulatory networks (GRNs) that regulate the synthesis of proteins. Advances in technology will undeniably lead us to more answers on the subject {{#pmid:22230617|PMID22230617}}.<br /> <br /> ===Embryonic origins===<br /> ----<br /> [[File:Trunk_NCC_migration.jpg|left|450px|thumb|Trunk NCC migration]]<br /> The adrenal gland is made up of the adrenal cortex and adrenal medulla, which both have different embryonic origins. The adrenal medulla arises from the neural crest tissue, found near the level of the coeliac plexus & sympathetic ganglion at somites 18-24 {{#pmid:16124976|PMID16124976}}. Specifically, this neural crest tissue comes from the trunk neural crest cells (see above figure to determine the approximate location in an embryo) <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> The trunk neural crest coordinates the development of the endocrine system, secretory cells, the peripheral nervous system and, to some degree, skeletal development, as well as innervation of the intestine {{#pmid: 28287247|PMID 28287247}}. The trunk neural cells arise caudally, undergo an epithelial to mesenchymal transition and follow three migratory pathways {{#pmid:20399766|PMID20399766}}.<br /> [[File:Differentiation_of_NCC.jpg|left|580px|thumb|Differentiation of chromaffin cells]]<br /> - A dorsolateral pathway (between ectoderm and somites), these become melanocytes, travel up to the point of the dermis and become a major part of the hair follicles and skin <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> - A ventrolateral pathway (through the somites)<br /> - A ventromedial pathway (between neural tube and posterior schlerotome){{#pmid:20399766|PMID20399766}}.<br /> <br /> Migration of neural crest cells from the sympathetic ganglion is what leads to the development of the adrenal medulla. In week 8 of development, immature cells called neuroblasts migrate through to the inner portion of the medulla, where they become the adrenal medulla {{#pmid:19683477|PMID19683477}}. Chromaffin cells are neuroendocrine cells and are found in the sympathetic ganglia and make up the majority of the adrenal medulla{{#pmid:19683477|PMID19683477}}. They synthesise and release a range of hormones in the body and arise from the temporary neural crest. The term chromaffin was inspired by the staining capacity of these cells when they came into contact with chrome salts. They make, store, export and use catecholamines, responsible for making noradrenaline and originate at the caudal region of somites 18-24 of the neural crest, also known as the adrenomedullary region {{#pmid:19683477|PMID19683477}}.<br /> <br /> For cells to leave the neural crest and begin their migration, certain conditions need to be met, that is, the cells need to be loosely connected, their tight junctions becoming relaxed, initiated by "Slug protein" and a loss of N-Cadherin which also leads to the loosening of these junctions. The surrounding matrix as well as chemotactic and stem cell factors of the neural tube are then what dictates how the neural crest cells move, some proteins stopping their migration to that area and others encouraging the movement <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. After splitting apart, the first neural crest cells move ventrally and pass into the spaces between the somites and then, through the anterior portions of each segment until they arrive at the para-aortic sites, where they become the cells of the sympathetic ganglia and the adrenal medulla {{#pmid:19683477|PMID19683477}}. BMP-4 (bone morphogenetic protein 4) then acts on these neural crest cells, preventing them from becoming cells that have a neural function and causing them to become chromaffin cells at the adrenal medulla. Glucocorticoids then play a role in maintenance of chromaffin cells in postnatal life, this was only found recently, as previously it was thought that glucocorticoids were responsible entirely for the differentiation of neural crest cells into chromaffin, or adrenomedullary cells {{#pmid:23220335|PMID23220335}}.<br /> <br /> ===Developmental time course===<br /> ----<br /> <br /> [[File:Adrenal_Medulla_Developmental_Timeline.jpg|right|thumb|500px]]<br /> <br /> The adrenal gland has two distinct sections, the cortex and the medulla, both with different embryonic origins. The cortex accounts for 90% of the adrenal glands and arises from intermediate mesoderm. The medulla only accounts for 10% of the adult adrenal glands, however it has neural crest embryonic origin. The medulla consists of chromaffinoblast cells which are migrant neuroblast cells from the neural crest, therefore the adrenal medulla is a component of the sympathetic nervous system.{{#pmid:21175739|PMID21175739}} Neural crest cells replicate in week 7 and begin to differentiate in week 8, the cells then migrate to the developing adrenal gland in week 9 of development.{{#pmid:25255746|PMID25255746}}{{#pmid:18279781|PMID18279781}} The neural crest cells infiltrate the cortex and the chromaffin cells are scattered islands in the cortex.{{#pmid:23354096|PMID23354096}} Throughout development the cells will become more compact in the centre of the gland, during this period of development the adrenal gland is growing rapidly. The gland is abnormally large until the second trimester and the medulla is much thicker prenatally.{{#pmid:18279781|PMID18279781}}{{#pmid:21175739|PMID21175739}}<br /> <br /> ===Developmental/adult function===<br /> ----<br /> ===Tissue and Organ structure===<br /> <br /> <br /> ====Normal Structure and Function of the Adrenal Medulla====<br /> <br /> The cells of the adrenal medulla are derived from the neural crest as opposed to the mesodermal origins of the cortex. The medulla contains secretory cells called chromaffin cells, due to the agents they produce when oxidised, such as chromate. These cells secrete epinephrine and norepinephrine in response to various substances such as acetylcholine.<br /> <br /> There are three types of cells in the adult adrenal medulla: <br /> 1) Epinephrine cells<br /> <br /> 2) Norepinephrine cells <br /> <br /> 3) Small granule-containing cells (SGCs)<br /> <br /> These cells also produce various other peptides such as substance P and neurotensin. The adrenal medulla also contains presynaptic sympathetic ganglion cells. {{#pmid:1694230|PMID1694230}}<br /> <br /> ====Related Anatomy====<br /> <br /> The tissue and organ structure of the adrenal medulla should be understood with regard to its specialised function within the sympathetic nervous system. <br /> <br /> The medullary region of the adrenal glands is tasked with the endocrine secretions of adrenaline and nor-adrenaline in response to environmental stressors that are signalled for by the sympathetic nervous system. That is, the secretion of fight-or-flight response hormones in order to restrict vasculature to the trunk and increase vascular activity in the peripheral musculature.<br /> <br /> The adrenal glands are supplied by several branches of the great vessels in the abdominal cavity. The secreted catecholamines in the medulla are directly able to pass to the blood stream this way.<br /> <br /> These adrenal glands and their contents are retroperitoneal in the adult and varied in shape, with the left often being semilunar and right being pyramidal. Nervous supply of the adrenal glands is achieved by contributions from the splanchnic nerves of the celiac plexus.<br /> <br /> <br /> ====Role of the Adrenal Medulla====<br /> <br /> Understanding the biochemistry of catecholamines is necessary to see how the adrenal medulla is designed in the stages of embryology and how it is suited for life in the neonate and adult. <br /> <br /> The epinephrine and norepinephrine in the neonate and adult work by primarily changing the osmoregulatory state of vasculature in organs. With the exclusion of their neuromodulatory and neurotransmitter functions, epinephrine and norepinephrine are mainly tasked with the control of sympathetic and parasympathetic supplies. <br /> <br /> Norepinephrine is a constrictor of peripheral vasculature by antagonising the action of surface receptors expressed on the endothelium of blood vessels, specifically Alpha-1 and Alpha-2 receptors, such that vascular resistance increases. <br /> <br /> Epinephrine is both a vasoconstrictor and vasodilator, depending on what receptors it attaches to. As a non-selective adrenergic agonist, it acts on Alpha-1, Alpha-2, Beta-1, Beta-2 and Beta-3 receptors that are found throughout the body's tissues, yielding many different physiological responses.<br /> <br /> <br /> [[File:Dd.jpg|500px|thumb|right|Adult Adrenal Glands in situ]] <br /> ----<br /> <br /> ===Molecular mechanisms/factors/genes===<br /> ----<br /> <br /> ====Genes and Transcription Factors Involved with the Adrenal Medulla's Development====<br /> <br /> Members of the SOX (SRY-Box) gene family have multiple key contributors to Neural Crest in the Adrenal Medulla.<br /> <br /> Mouse models have demonstrated that SOX-10 knock-outs (mice whose DNA has been engineered to not express SOX-10) do not have an adrenal medulla. There has also been suggestion that SOX-8,9 and 10 are all strongly related to the migratory patterning of neural crest cells to the developing adrenal glands.<br /> <br /> The TH gene (for Tyrosine Hydroxylase) encodes the aforementioned enzyme in the adrenal medulla and central nervous system. Tyrosine Hydroxylase is crucial in biochemical pathways and cascades for the synthesis of catecholamines and other CNS neurotransmitters. The conversion from L-Tyrosine to L-DOPA is dependent upon the catalytic action of Tyrosine Hydroxylase. From there, L-DOPA can make Dopamine and eventually Epinephrine and Norepinephrine as well. <br /> <br /> [[File:Catecholamine_Synthesis.jpg|500px|thumb|right|Cascade of Catecholamine Synthesis]]<br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2291442/<br /> https://www.ncbi.nlm.nih.gov/pubmed/19396395<br /> <br /> ===Abnormalities/abnormal development===<br /> ----<br /> ===Animal models===<br /> ----<br /> Animal models are an integral part of research in embryology. In particular due to the moral concerns regarding the use of humans in scientific research. As a result different animals are used as substitutes to simulate the same environments and hope to achieve results that would also be able to represent humans as well. Prenatal adrenal gland development has been described in a number of scientific reports dating from the 1900s to studies in more recent years. These involved a variety of animal models such as ox, sheep, swine and most commonly mice. <br /> <br /> ====Chromaffin cells (in rat models)====<br /> There has been extensive research conducted into the adrenal chromaffin cells and their embryological developments. As explained above nueral crest cells are pluripotent meaning they are able to differentiate into multiple different cells. The neural crest cells give rise to chromaffin cells of the adrenal medulla.<br /> <br /> To study the formation process of the adrenal medulla in the embryonic period, we visualized chromaffin cells of rat embryos at 13 to 17 days of gestation using anti-tyrosine hydroxylase (TH) antiserum, and created three-dimensional images from serial tissue sections. Between 13 and 15 days of gestation, TH-positive cells (chromaffin cells) migrated from a group of TH-positive cells present dorsal to the adrenal primordium via the medial cranial end of the adrenal primordium into the adrenal primordium. At or after 16 days of gestation, the adrenal capsule was formed except on the ventral aspect of the cranial end of the adrenal gland, from which TH-positive cells penetrated into the adrenal gland.(Pubmed: 15240937) <br /> <br /> Past research has reported that nueral crest cells <br /> migrate into sympathetic ganglia and the adrenal cortex and almost completely convert t chromaffin cells by 19 days of gestation, forming the adrenal medulla. Since TH is used in this study as an indicator of chromaffin cells (adrenal medullary cells) is an enzyme involved in the early stage of the synthetic pathway of adrenaline and noradrenaline, the TH - positive cells observed in this study may include not only chromaffin cells but also sympathetic ganglion cells and SIF cells.<br /> It was previously thught that when neural crest - derived cells migrated via the sympatheti chain gangli into the adrenal gland or preaortic ganglion, they took different pathways to the respective destination at the time of passage through the ganglia of the sympathetic trunk.<br /> However, the reconstructed images in this study showed that the pathway of neural crest - deriveed cells from the ganglia of the sympathetic trunk to the adrenal medulla overlapped with the pathway to the preaortic ganglion. We speculate that neural crest cells use the same pathway to migrate to the ganglia of the sympathetic trunk, to the adrenal gland, and to the preaortic ganglion, this onclusion is good agreement of the suggestion by Ahoren. <br /> Ahonen suggested that some neural crest cells continue migration from the chain ganglia to the lateral sides of aorta, where they form the perirenal ganglia and adrenal medulla, and finally to the ventral side of the aorta to form the preaortic sympathetic tissue. However, that report only showed the several transverse sections of the fetal trunk for the a demonstration of the migration route of neural crest cells. In this study, using three dimensional reconstructed images, we aimed to observe how TH-labeled chromaffin cells penetrate into the adrenal anlage to form the adrenal medulla and whether the migration route of TH - positive cells from the adrenal connects the preaortic sympathetic ganglia <br /> (M.Yamato, R. Yanai, K. Arishima, 2004) <br /> <br /> Prenatal adrenal gland development has been described in numerous published reports covering a wide variety of species, including the ox (Katznelson, 1966; Wrobel and Suss, 1999), sheep (Davies, 1950; Wintour et al., 1975; Upadhyay and Zamboni, 1982; Naaman‐Reperant and Durand, 1997; Grino, 2004), swine (Sokolov et al., 2006) and mouse (Waring, 1935; Ikeda et al., 1994; Sass, 1996; Nyska and Maronpot, 1999; Bland et al., 2003; Val et al., 2007). Adrenal gland development also has been extensively described for humans as well (Kolliker, 1879; Minot, 1892; Zuckerkandl, 1912; Wieman, 1920; Ikeda et al., 1981; Langlois et al., 2002; Hanley and Arit, 2006).<br /> <br /> https://www.sciencedirect.com/science/article/pii/S0925477302004550<br /> http://dev.biologists.org/content/develop/126/13/2935.full.pdf<br /> <br /> ===Current research (labs)===<br /> ----<br /> The findings presented until now have focused on the mechanisms controlling migration along the dorsolateral path. In comparison, our understanding of the mechanisms controlling NCC migration along the ventral path are complicated by the fact that this population comprises multiple precursors that form different derivatives in distinct regions of the embryo. For example, ventrally migrating NCCs either stop within the sclerotome in close association with the neural tube to form neurons and glia of the sensory nervous system (i.e. the dorsal root ganglia [DRG]), while other NCCs continue to migrate further ventrally to form the autonomic nervous system (i.e. sympathetic ganglia and chromaffin cells of the adrenal gland)<br /> <br /> Adrenomedullary chromaffin cells are catecholamine (CA)-producing cells originating from trunk neural crest (NC) via sympathoadrenal progenitors (SAPs). We generated NC and SAPs from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) in vitro via BMP2/FGF2 exposure, ascertained by qPCR and immunoexpression of SOX10, ASCL1, TFAP2α, and PHOX2B, and by fluorescence-activated cell sorting selection for p75NTR and GD2, and confirmed their trunk-like HOX gene expression. We showed that continuing BMP4 and curtailing FGF2 in vitro, augmented with corticosteroid mimetic, induced these cells to upregulate the chromaffin cell-specific marker PNMT and other CA synthesis and storage markers, and we demonstrated noradrenaline and adrenaline by Faglu and high-performance liquid chromatography. We showed these human cells' SAP-like property of migration and differentiation into cells expressing chromaffin cell markers by implanting them into avian embryos in vivo and in chorio-allantoic membrane grafts. These cells have the potential for investigating differentiation of human chromaffin cells and for modeling diseases involving this cell type.<br /> <br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768882/<br /> <br /> ===Glossary===<br /> ----<br /> ===Reference list===</div>

Z5091101 https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z5091101&diff=356735 User:Z5091101 2018-10-11T02:57:34Z

<p>Z5091101: </p> <hr /> <div><br /> {{Editing Links}}<br /> <br /> <br /> Student REVIEWS:<br /> Melanocytes<br /> Peer review:<br /> Hello. I have had a look at your project and it seems your group is doing really well overall. There seems to be some missing information on the skin, I assume you are still researching that and collating your information. The use of images throughout is excellent, all your images are properly referenced and a good example to learn from. I cannot really suggest anything at this point apart from to keep researching and get going with the missing sections.<br /> <br /> Group 4: cardiac<br /> [[User:Z5091101|Z5091101]] ([[User talk:Z5091101|talk]]) 20:10, 3 October 2018 (AEST)z5091101[[User:Z5091101|Z5091101]] ([[User talk:Z5091101|talk]]) 20:10, 3 October 2018 (AEST)<br /> This project is coming along very well. Perhaps consider using a few more references as your list seems short. Also, I did like the use of a video but ideally it should be very short. I don't feel that many people will actually watch a 9 minute video. Perhaps a stop motion clip or a flow chart summary could replace this to make it easy to understand? Overall this is great work and seems to be a rather complex topic. Keep it up group 4.<br /> <br /> Group 5:DRG<br /> [User:Z5091101|Z5091101]] ([[User talk:Z5091101|talk]]) 20:14, 3 October 2018 (AEST)z5091101[[User:Z5091101|Z5091101]] ([[User talk:Z5091101|talk]]) 20:14, 3 October 2018 (AEST)<br /> There has been an extensive use of references which is great especially since this topic seems to be really complex. Maybe a few more images for the beginning part of the article will make it look more user-friendly. Definitely have a look over for any grammar/spelling issues.<br /> <br /> <br /> [[File:Neuropore cell shape changes.png|400px]]<br /> <br /> Neuropore cell shape changes{{#pmid:30064364|PMID30064364}}<br /> <br /> <br /> <references/><br /> <br /> ==Reference==<br /> PMID: 30056110<br /> <br /> <br /> {{#pmid:30056110}}<br /> <br /> <br /> <br /> In vitro maturation recent article{{#pmid:30056110|30056110}}<br /> <br /> [[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 13:33, 31 July 2018 (AEST) You have left out the second PMID, see correct code below:<br /> <br /> <nowiki>{{#pmid:30056110|PMID30056110}}</nowiki></div>

Z5091101 https://embryology.med.unsw.edu.au/embryology/index.php?title=File:Differentiation_of_NCC.jpg&diff=356687 File:Differentiation of NCC.jpg 2018-10-10T07:38:39Z

<p>Z5091101: </p> <hr /> <div>The neural crest cells become chromaffin precursor cells under exposure to BMP-4, and their growth and postnatal health is maintained by the secretion of glucocorticoids.<br /> <br /> <br /> This image was inspired by the following figure on the link below, however the information was altered slightly, due to recent studies showing that glucocorticoids do not initially cause neural crest cells to become chromaffin cells, but rather BMP-4 protein{{#pmid:23220335|PMID23220335}}:<br /> https://www.ncbi.nlm.nih.gov/books/NBK10065/figure/A3132/?report=objectonly <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>.</div>

Z5091101 https://embryology.med.unsw.edu.au/embryology/index.php?title=File:Differentiation_of_NCC.jpg&diff=356685 File:Differentiation of NCC.jpg 2018-10-10T07:37:41Z

<p>Z5091101: </p> <hr /> <div>The neural crest cells become chromaffin precursor cells under exposure to BMP-4, and their growth and postnatal health is maintained by the secretion of glucocorticoids.<br /> <br /> <br /> This image was inspired by the following figure on the link below, however the information was altered slightly, due to recent studies showing that glucocorticoids do not initially cause neural crest cells to become chromaffin cells, but rather BMP-4 protein{{#pmid:23220335|PMID23220335}}:<br /> https://www.ncbi.nlm.nih.gov/books/NBK10065/figure/A3132/?report=objectonly</div>

Z5091101 https://embryology.med.unsw.edu.au/embryology/index.php?title=2018_Group_Project_1&diff=356683 2018 Group Project 1 2018-10-10T07:34:36Z

<p>Z5091101: /* Embryonic origins */</p> <hr /> <div>=The Contribution of Neural Crest Cells to the Adrenal Medulla=<br /> ----<br /> {{2018ANAT2341ProjectHeader}}<br /> <br /> <br /> ===Introduction===<br /> [[User:Z5014972|Z5014972]] ([[User talk:Z5014972|talk]]) 12:47, 14 August 2018 (AEST)z5014972 <br /> good review article https://link.springer.com/article/10.1007%2Fs12022-009-9070-6<br /> ----<br /> <br /> <br /> The neural crest of an embryo differentiates and migrates to form various components of the body. One of these tissues is the medulla of the adrenal gland which is involved in the production of adrenalin and noradrenalin. This project will comprehensively outline the history of neural crest research, the embryonic developmental time course, tissue and organ structure, molecular mechanisms, abnormalities, animal models and current research.<br /> <br /> ===History===<br /> ----<br /> '''Describing the neural crest'''<br /> [[File:Wilhelm_His_History_Wilhelm.jpeg|left|230px|thumb|Wilhelm His]]<br /> The "neural crest" is a structure in the embryo and is the junction between the neural and epidermal ectoderm. It is exclusive to vertebrates and forms a range of structures{{#pmid:22230617|PMID22230617}}. The neural crest contributes a large number of cells of varying structure and function that directly or indirectly contribute to the development of tissues and organs within the body {{#pmid:19179766|PMID19179766}}. In 1868, the neural crest cells were first identified in a chick embryo as a collection of cells known as "Zwischenstrang" by Professor Wilhelm His {{#pmid:22820859|PMID22820859}}. Wilhelm His was among the first to provide an explanation for the mechanics governing the developing embryo as well as the physiology and the organs that the differing germinal regions would eventually give rise to. In 1878, the term neural ridge was used to describe this collection of cells but the term neural crest was later coined by Arthur Milnes Marshall in 1879 in a paper he worked on disseminating the knowledge from his research on the development of cranial nerves in chicken embryos. {{#pmid:19179766|PMID19179766}}.<br /> [[File:NC Location.jpg|left|450px|thumb|The neural crest]]<br /> <br /> '''1890s-1950s'''<br /> The neural crest is the point of origin for spinal/cranial ganglia and neurons. This theory received little criticism and was not contested much by other researchers prior to the 1890s. This is owing to the fact that the neural crest is quite closely related to the neural tube and thus this relationship makes sense. This discovery was made by His and Marshall, however, they found this out independently of one another.In the 1890s, Julia Platt, claimed that odontoblasts as well as the cartilages forming the facial and pharyngeal arch skeletons came from the ectoderm. This created much debate and was contested by many{{#pmid:22820859|PMID22820859}}. <br /> <br /> This is because this theory completely contradicted the germ-layer theory, whereby skeletal tissues originate at the mesoderm and not the ectoderm. The controversies this finding created brought about a slowing down of research, as demonstrated by a gap of almost 40 years between the theory that skeletal tissues originating from the neural crest. Today, it is known that the neural crest does indeed play a role in the development of the skeleton in vertebrates, particularly, the cranial neural crest. Although these studies were occurring, the focus was still primarily on researching pigment cells and ganglia of the spine up until the 1950s, when Sven Hörstadius' major work on the neural crest was published, titled "The Neural Crest: Its properties and derivatives in the light of experimental research". This work focused on experimental data tracing the development of the cartilaginous skeleton derived from the neural crest {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1960s - 1970s'''<br /> In the 1960s, the migration patterns of neural crest cells were studied in avian embryos (birds). This was a shift from studying the embryos of amphibians. This was inspired by studies conducted in the 1960s on neural crest cells migrating from the brain and spinal cord, known as trunk and cranial neural crest cells {{#pmid:19179766|PMID19179766}}. The cranial neural crest eventually becomes the bones, cartilage and connective tissues forming the foundation of the face, ears and teeth. The trunk neural crest cells can either become melanocytes or can migrate into sclerotomes which are later contributors to the cartilage of the spine and the dorsal root ganglia {{#pmid:22820859|PMID22820859}}. The cells in the trunk neural crest that migrate vertically become the sympathetic ganglia, the nerves proximal to the aorta and the adrenal medulla <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. In the 1970s many detailed maps signifying the pathways of many of the neural crest cells appeared as well as an understanding that the environment in which the neural crest cells are found plays a major role in their final development as well as the occurrences of abnormalities in the fetus {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1980s - 21st century'''<br /> [[File:Regions_of_NC_Cells.jpg|left|Neural crest regions|thumb]]<br /> From the 1980s-1990s, the causative agent of organ transformation from one to another (homeotic patterning), as well as the Hox genes which regulate the axis of most symmetrical animal embryos were founded and studied. The neural crest, which previously was divided into the cranial and trunk regions, was now further divided into the vagal and sacral neural crest, the cardiac neural crest and the cephalic neural crest {{#pmid:19179766|PMID19179766}}. The vagal & sacral neural crest gives rise to the parasympathetic ganglia found in the gut. Without these ganglia, peristalsis, is not possible <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. The cardiac neural crest contributes to the valves, septa and major blood vessels of the heart, as well as connective tissues and cartilage{{#pmid:19179766|PMID19179766}}. This is important for the structure of the heart as well as its overall function, enabling it to move blood around the body efficiently as well as keep pulmonary and aortic circulation separated <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> <br /> <br /> Today, knowledge of the neural crest cells, their migration patterns, modes of differentiation, derivatives and apoptosis (cell death) are being studied extensively. This is being done on a comparative basis between different organisms, to add further evidence for evolution {{#pmid:19179766|PMID19179766}}. The neural crest is definitely forging a "crest" between the fields of developmental and evolutionary biology, as it is a structure '''shared exclusively by all vertebrates'''. Invertebrates do not derive their specialised cells from the neural crest as they do not have one, rather, they derive these from the endomesoderm {{#pmid:22230617|PMID22230617}}.<br /> <br /> '''Future directions'''<br /> <br /> Since its discovery by His, the neural crest field has made great progress, from studies performed on the structure, to analysis of the molecules and whether certain aspects of the neural crest are specific to a single species of organism, or to all vertebrates collectively. Future work on the cranial neural crest needs to be done as well as identifying and categorising the networks responsible for the proliferation and death of cells, as well as how the cells move and migrate, as well as the gene regulatory networks (GRNs) that regulate the synthesis of proteins. Advances in technology will undeniable lead us to more answers on the subject {{#pmid:22230617|PMID22230617}}.<br /> <br /> ===Embryonic origins===<br /> ----<br /> [[File:Trunk_NCC_migration.jpg|left|450px|thumb|Trunk NCC migration]]<br /> The adrenal gland is made up of the adrenal cortex and adrenal medulla, which both have different embryonic origins. The adrenal medulla arises from the neural crest tissue, found near the level of the coeliac plexus & sympathetic ganglion at somites 18-24 {{#pmid:16124976|PMID16124976}}. Specifically, this neural crest tissue comes from the trunk neural crest cells (see above figure to determine the approximate location in an embryo) <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> The trunk neural crest coordinates the development of the endocrine system, secretory cells, the peripheral nervous system and, to some degree, skeletal development, as well as innervation of the intestine {{#pmid: 28287247|PMID 28287247}}. The trunk neural cells arise caudally, undergo an epithelial to mesenchymal transition and follow three migratory pathways {{#pmid:20399766|PMID20399766}}.<br /> [[File:Differentiation_of_NCC.jpg|left|580px|thumb|Differentiation of chromaffin cells]]<br /> - A dorsolateral pathway (between ectoderm and somites), these become melanocytes, travel up to the point of the dermis and become a major part of the hair follicles and skin <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> - A ventrolateral pathway (through the somites)<br /> - A ventromedial pathway (between neural tube and posterior schlerotome){{#pmid:20399766|PMID20399766}}.<br /> <br /> Migration of neural crest cells from the sympathetic ganglion is what leads to the development of the adrenal medulla. In week 8 of development, immature cells called neuroblasts migrate through to the inner portion of the medulla, where they become the adrenal medulla {{#pmid:19683477|PMID19683477}}. Chromaffin cells are neuroendocrine cells and are found in the sympathetic ganglia and make up the majority of the adrenal medulla{{#pmid:19683477|PMID19683477}}. They synthesise and release a range of hormones in the body and arise from the temporary neural crest. The term chromaffin was inspired by the staining capacity of these cells when they came into contact with chrome salts. They make, store, export and use catecholamines, responsible for making noradrenaline and originate at the caudal region of somites 18-24 of the neural crest, also known as the adrenomedullary region {{#pmid:19683477|PMID19683477}}.<br /> <br /> For cells to leave the neural crest and begin their migration, certain conditions need to be met, that is, the cells need to be loosely connected, their tight junctions becoming relaxed, initiated by "Slug protein" and a loss of N-Cadherin which also leads to the loosening of these junctions. The surrounding matrix as well as chemotactic and stem cell factors of the neural tube are then what dictates how the neural crest cells move, some proteins stopping their migration to that area and others encouraging the movement <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. After splitting apart, the first neural crest cells move ventrally and pass into the spaces between the somites and then, through the anterior portions of each segment until they arrive at the para-aortic sites, where they become the cells of the sympathetic ganglia and the adrenal medulla {{#pmid:19683477|PMID19683477}}. BMP-4 (bone morphogenetic protein 4) then acts on these neural crest cells, preventing them from becoming cells that have a neural function and causing them to become chromaffin cells at the adrenal medulla. Glucocorticoids then play a role in maintenance of chromaffin cells in postnatal life, this was only found recently, as previously it was thought that glucocorticoids were responsible entirely for the differentiation of neural crest cells into chromaffin, or adrenomedullary cells {{#pmid:23220335|PMID23220335}}.<br /> <br /> ===Developmental time course===<br /> ----<br /> <br /> [[File:Adrenal_Medulla_Developmental_Timeline.jpg|right|thumb|500px]]<br /> <br /> The adrenal gland has two distinct sections, the cortex and the medulla, both with different embryonic origins. The cortex accounts for 90% of the adrenal glands and arises from intermediate mesoderm. The medulla only accounts for 10% of the adult adrenal glands, however it has neural crest embryonic origin. The medulla consists of chromaffinoblast cells which are migrant neuroblast cells from the neural crest, therefore the adrenal medulla is a component of the sympathetic nervous system.{{#pmid:21175739|PMID21175739}} Neural crest cells replicate in week 7 and begin to differentiate in week 8, the cells then migrate to the developing adrenal gland in week 9 of development.{{#pmid:25255746|PMID25255746}}{{#pmid:18279781|PMID18279781}} The neural crest cells infiltrate the cortex and the chromaffin cells are scattered islands in the cortex.{{#pmid:23354096|PMID23354096}} Throughout development the cells will become more compact in the centre of the gland, during this period of development the adrenal gland is growing rapidly. The gland is abnormally large until the second trimester and the medulla is much thicker prenatally.{{#pmid:18279781|PMID18279781}}{{#pmid:21175739|PMID21175739}}<br /> <br /> ===Developmental/adult function===<br /> ----<br /> ===Tissue and Organ structure===<br /> <br /> <br /> ====Normal Structure and Function of the Adrenal Medulla====<br /> <br /> The cells of the adrenal medulla are derived from the neural crest as opposed to the mesodermal origins of the cortex. The medulla contains secretory cells called chromaffin cells, due to the agents they produce when oxidised, such as chromate. These cells secrete epinephrine and norepinephrine in response to various substances such as acetylcholine.<br /> <br /> There are three types of cells in the adult adrenal medulla: <br /> 1) Epinephrine cells<br /> <br /> 2) Norepinephrine cells <br /> <br /> 3) Small granule-containing cells (SGCs)<br /> <br /> These cells also produce various other peptides such as substance P and neurotensin. The adrenal medulla also contains presynaptic sympathetic ganglion cells. {{#pmid:1694230|PMID1694230}}<br /> <br /> ====Related Anatomy====<br /> <br /> The tissue and organ structure of the adrenal medulla should be understood with regard to its specialised function within the sympathetic nervous system. <br /> <br /> The medullary region of the adrenal glands is tasked with the endocrine secretions of adrenaline and nor-adrenaline in response to environmental stressors that are signalled for by the sympathetic nervous system. That is, the secretion of fight-or-flight response hormones in order to restrict vasculature to the trunk and increase vascular activity in the peripheral musculature.<br /> <br /> The adrenal glands are supplied by several branches of the great vessels in the abdominal cavity. The secreted catecholamines in the medulla are directly able to pass to the blood stream this way.<br /> <br /> These adrenal glands and their contents are retroperitoneal in the adult and varied in shape, with the left often being semilunar and right being pyramidal. Nervous supply of the adrenal glands is achieved by contributions from the splanchnic nerves of the celiac plexus.<br /> <br /> <br /> ====Role of the Adrenal Medulla====<br /> <br /> Understanding the biochemistry of catecholamines is necessary to see how the adrenal medulla is designed in the stages of embryology and how it is suited for life in the neonate and adult. <br /> <br /> The epinephrine and norepinephrine in the neonate and adult work by primarily changing the osmoregulatory state of vasculature in organs. With the exclusion of their neuromodulatory and neurotransmitter functions, epinephrine and norepinephrine are mainly tasked with the control of sympathetic and parasympathetic supplies. <br /> <br /> Norepinephrine is a constrictor of peripheral vasculature by antagonising the action of surface receptors expressed on the endothelium of blood vessels, specifically Alpha-1 and Alpha-2 receptors, such that vascular resistance increases. <br /> <br /> Epinephrine is both a vasoconstrictor and vasodilator, depending on what receptors it attaches to. As a non-selective adrenergic agonist, it acts on Alpha-1, Alpha-2, Beta-1, Beta-2 and Beta-3 receptors that are found throughout the body's tissues, yielding many different physiological responses.<br /> <br /> <br /> [[File:Dd.jpg|500px|thumb|right|Adult Adrenal Glands in situ]] <br /> ----<br /> <br /> ===Molecular mechanisms/factors/genes===<br /> ----<br /> <br /> ====Genes and Transcription Factors Involved with the Adrenal Medulla's Development====<br /> <br /> Members of the SOX (SRY-Box) gene family have multiple key contributors to Neural Crest in the Adrenal Medulla.<br /> <br /> Mouse models have demonstrated that SOX-10 knock-outs (mice whose DNA has been engineered to not express SOX-10) do not have an adrenal medulla. There has also been suggestion that SOX-8,9 and 10 are all strongly related to the migratory patterning of neural crest cells to the developing adrenal glands.<br /> <br /> The TH gene (for Tyrosine Hydroxylase) encodes the aforementioned enzyme in the adrenal medulla and central nervous system. Tyrosine Hydroxylase is crucial in biochemical pathways and cascades for the synthesis of catecholamines and other CNS neurotransmitters. The conversion from L-Tyrosine to L-DOPA is dependent upon the catalytic action of Tyrosine Hydroxylase. From there, L-DOPA can make Dopamine and eventually Epinephrine and Norepinephrine as well. <br /> <br /> [[File:Catecholamine_Synthesis.jpg|500px|thumb|right|Cascade of Catecholamine Synthesis]]<br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2291442/<br /> https://www.ncbi.nlm.nih.gov/pubmed/19396395<br /> <br /> ===Abnormalities/abnormal development===<br /> ----<br /> ===Animal models===<br /> ----<br /> Animal models are an integral part of research in embryology. In particular due to the moral concerns regarding the use of humans in scientific research. As a result different animals are used as substitutes to simulate the same environments and hope to achieve results that would also be able to represent humans as well. Prenatal adrenal gland development has been described in a number of scientific reports dating from the 1900s to studies in more recent years. These involved a variety of animal models such as ox, sheep, swine and most commonly mice. <br /> <br /> ====Chromaffin cells =(in rat models)====<br /> There has been extensive research conducted into the adrenal chromaffin cells and their embryological developments. As explained above nueral crest cells are pluripotent meaning they are able to differentiate into multiple different cells. The neural crest cells give rise to chromaffin cells of the adrenal medulla.<br /> <br /> To study the formation process of the adrenal medulla in the embryonic period, we visualized chromaffin cells of rat embryos at 13 to 17 days of gestation using anti-tyrosine hydroxylase (TH) antiserum, and created three-dimensional images from serial tissue sections. Between 13 and 15 days of gestation, TH-positive cells (chromaffin cells) migrated from a group of TH-positive cells present dorsal to the adrenal primordium via the medial cranial end of the adrenal primordium into the adrenal primordium. At or after 16 days of gestation, the adrenal capsule was formed except on the ventral aspect of the cranial end of the adrenal gland, from which TH-positive cells penetrated into the adrenal gland.(Pubmed: 15240937) <br /> <br /> Ahonen suggested that some neural crest cells continue migration from the chain ganglia to the lateral sides of aorta, where they form the perirenal ganglia and adrenal medulla, and finally to the ventral side of the aorta to form the preaortic sympathetic tissue. However, that report only showed the several transverse sections of the fetal trunk for the a demonstration of the migration route of neural crest cells. In this study, using three dimensional reconstructed images, we aimed to observe how TH-labeled chromaffin cells penetrate into the adrenal anlage to form the adrenal medulla and whether the migration route of TH - positive cells from the adrenal connects the preaortic sympathetic ganglia <br /> (M.Yamato, R. Yanai, K. Arishima, 2004) <br /> <br /> Prenatal adrenal gland development has been described in numerous published reports covering a wide variety of species, including the ox (Katznelson, 1966; Wrobel and Suss, 1999), sheep (Davies, 1950; Wintour et al., 1975; Upadhyay and Zamboni, 1982; Naaman‐Reperant and Durand, 1997; Grino, 2004), swine (Sokolov et al., 2006) and mouse (Waring, 1935; Ikeda et al., 1994; Sass, 1996; Nyska and Maronpot, 1999; Bland et al., 2003; Val et al., 2007). Adrenal gland development also has been extensively described for humans as well (Kolliker, 1879; Minot, 1892; Zuckerkandl, 1912; Wieman, 1920; Ikeda et al., 1981; Langlois et al., 2002; Hanley and Arit, 2006).<br /> <br /> https://www.sciencedirect.com/science/article/pii/S0925477302004550<br /> http://dev.biologists.org/content/develop/126/13/2935.full.pdf<br /> <br /> ===Current research (labs)===<br /> ----<br /> The findings presented until now have focused on the mechanisms controlling migration along the dorsolateral path. In comparison, our understanding of the mechanisms controlling NCC migration along the ventral path are complicated by the fact that this population comprises multiple precursors that form different derivatives in distinct regions of the embryo. For example, ventrally migrating NCCs either stop within the sclerotome in close association with the neural tube to form neurons and glia of the sensory nervous system (i.e. the dorsal root ganglia [DRG]), while other NCCs continue to migrate further ventrally to form the autonomic nervous system (i.e. sympathetic ganglia and chromaffin cells of the adrenal gland)<br /> <br /> Adrenomedullary chromaffin cells are catecholamine (CA)-producing cells originating from trunk neural crest (NC) via sympathoadrenal progenitors (SAPs). We generated NC and SAPs from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) in vitro via BMP2/FGF2 exposure, ascertained by qPCR and immunoexpression of SOX10, ASCL1, TFAP2α, and PHOX2B, and by fluorescence-activated cell sorting selection for p75NTR and GD2, and confirmed their trunk-like HOX gene expression. We showed that continuing BMP4 and curtailing FGF2 in vitro, augmented with corticosteroid mimetic, induced these cells to upregulate the chromaffin cell-specific marker PNMT and other CA synthesis and storage markers, and we demonstrated noradrenaline and adrenaline by Faglu and high-performance liquid chromatography. We showed these human cells' SAP-like property of migration and differentiation into cells expressing chromaffin cell markers by implanting them into avian embryos in vivo and in chorio-allantoic membrane grafts. These cells have the potential for investigating differentiation of human chromaffin cells and for modeling diseases involving this cell type.<br /> <br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768882/<br /> <br /> ===Glossary===<br /> ----<br /> ===Reference list===</div>

Z5091101 https://embryology.med.unsw.edu.au/embryology/index.php?title=2018_Group_Project_1&diff=356681 2018 Group Project 1 2018-10-10T07:33:50Z

<p>Z5091101: /* Embryonic origins */</p> <hr /> <div>=The Contribution of Neural Crest Cells to the Adrenal Medulla=<br /> ----<br /> {{2018ANAT2341ProjectHeader}}<br /> <br /> <br /> ===Introduction===<br /> [[User:Z5014972|Z5014972]] ([[User talk:Z5014972|talk]]) 12:47, 14 August 2018 (AEST)z5014972 <br /> good review article https://link.springer.com/article/10.1007%2Fs12022-009-9070-6<br /> ----<br /> <br /> <br /> The neural crest of an embryo differentiates and migrates to form various components of the body. One of these tissues is the medulla of the adrenal gland which is involved in the production of adrenalin and noradrenalin. This project will comprehensively outline the history of neural crest research, the embryonic developmental time course, tissue and organ structure, molecular mechanisms, abnormalities, animal models and current research.<br /> <br /> ===History===<br /> ----<br /> '''Describing the neural crest'''<br /> [[File:Wilhelm_His_History_Wilhelm.jpeg|left|230px|thumb|Wilhelm His]]<br /> The "neural crest" is a structure in the embryo and is the junction between the neural and epidermal ectoderm. It is exclusive to vertebrates and forms a range of structures{{#pmid:22230617|PMID22230617}}. The neural crest contributes a large number of cells of varying structure and function that directly or indirectly contribute to the development of tissues and organs within the body {{#pmid:19179766|PMID19179766}}. In 1868, the neural crest cells were first identified in a chick embryo as a collection of cells known as "Zwischenstrang" by Professor Wilhelm His {{#pmid:22820859|PMID22820859}}. Wilhelm His was among the first to provide an explanation for the mechanics governing the developing embryo as well as the physiology and the organs that the differing germinal regions would eventually give rise to. In 1878, the term neural ridge was used to describe this collection of cells but the term neural crest was later coined by Arthur Milnes Marshall in 1879 in a paper he worked on disseminating the knowledge from his research on the development of cranial nerves in chicken embryos. {{#pmid:19179766|PMID19179766}}.<br /> [[File:NC Location.jpg|left|450px|thumb|The neural crest]]<br /> <br /> '''1890s-1950s'''<br /> The neural crest is the point of origin for spinal/cranial ganglia and neurons. This theory received little criticism and was not contested much by other researchers prior to the 1890s. This is owing to the fact that the neural crest is quite closely related to the neural tube and thus this relationship makes sense. This discovery was made by His and Marshall, however, they found this out independently of one another.In the 1890s, Julia Platt, claimed that odontoblasts as well as the cartilages forming the facial and pharyngeal arch skeletons came from the ectoderm. This created much debate and was contested by many{{#pmid:22820859|PMID22820859}}. <br /> <br /> This is because this theory completely contradicted the germ-layer theory, whereby skeletal tissues originate at the mesoderm and not the ectoderm. The controversies this finding created brought about a slowing down of research, as demonstrated by a gap of almost 40 years between the theory that skeletal tissues originating from the neural crest. Today, it is known that the neural crest does indeed play a role in the development of the skeleton in vertebrates, particularly, the cranial neural crest. Although these studies were occurring, the focus was still primarily on researching pigment cells and ganglia of the spine up until the 1950s, when Sven Hörstadius' major work on the neural crest was published, titled "The Neural Crest: Its properties and derivatives in the light of experimental research". This work focused on experimental data tracing the development of the cartilaginous skeleton derived from the neural crest {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1960s - 1970s'''<br /> In the 1960s, the migration patterns of neural crest cells were studied in avian embryos (birds). This was a shift from studying the embryos of amphibians. This was inspired by studies conducted in the 1960s on neural crest cells migrating from the brain and spinal cord, known as trunk and cranial neural crest cells {{#pmid:19179766|PMID19179766}}. The cranial neural crest eventually becomes the bones, cartilage and connective tissues forming the foundation of the face, ears and teeth. The trunk neural crest cells can either become melanocytes or can migrate into sclerotomes which are later contributors to the cartilage of the spine and the dorsal root ganglia {{#pmid:22820859|PMID22820859}}. The cells in the trunk neural crest that migrate vertically become the sympathetic ganglia, the nerves proximal to the aorta and the adrenal medulla <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. In the 1970s many detailed maps signifying the pathways of many of the neural crest cells appeared as well as an understanding that the environment in which the neural crest cells are found plays a major role in their final development as well as the occurrences of abnormalities in the fetus {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1980s - 21st century'''<br /> [[File:Regions_of_NC_Cells.jpg|left|Neural crest regions|thumb]]<br /> From the 1980s-1990s, the causative agent of organ transformation from one to another (homeotic patterning), as well as the Hox genes which regulate the axis of most symmetrical animal embryos were founded and studied. The neural crest, which previously was divided into the cranial and trunk regions, was now further divided into the vagal and sacral neural crest, the cardiac neural crest and the cephalic neural crest {{#pmid:19179766|PMID19179766}}. The vagal & sacral neural crest gives rise to the parasympathetic ganglia found in the gut. Without these ganglia, peristalsis, is not possible <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. The cardiac neural crest contributes to the valves, septa and major blood vessels of the heart, as well as connective tissues and cartilage{{#pmid:19179766|PMID19179766}}. This is important for the structure of the heart as well as its overall function, enabling it to move blood around the body efficiently as well as keep pulmonary and aortic circulation separated <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> <br /> <br /> Today, knowledge of the neural crest cells, their migration patterns, modes of differentiation, derivatives and apoptosis (cell death) are being studied extensively. This is being done on a comparative basis between different organisms, to add further evidence for evolution {{#pmid:19179766|PMID19179766}}. The neural crest is definitely forging a "crest" between the fields of developmental and evolutionary biology, as it is a structure '''shared exclusively by all vertebrates'''. Invertebrates do not derive their specialised cells from the neural crest as they do not have one, rather, they derive these from the endomesoderm {{#pmid:22230617|PMID22230617}}.<br /> <br /> '''Future directions'''<br /> <br /> Since its discovery by His, the neural crest field has made great progress, from studies performed on the structure, to analysis of the molecules and whether certain aspects of the neural crest are specific to a single species of organism, or to all vertebrates collectively. Future work on the cranial neural crest needs to be done as well as identifying and categorising the networks responsible for the proliferation and death of cells, as well as how the cells move and migrate, as well as the gene regulatory networks (GRNs) that regulate the synthesis of proteins. Advances in technology will undeniable lead us to more answers on the subject {{#pmid:22230617|PMID22230617}}.<br /> <br /> ===Embryonic origins===<br /> ----<br /> <br /> The adrenal gland is made up of the adrenal cortex and adrenal medulla, which both have different embryonic origins. The adrenal medulla arises from the neural crest tissue, found near the level of the coeliac plexus & sympathetic ganglion at somites 18-24 {{#pmid:16124976|PMID16124976}}. Specifically, this neural crest tissue comes from the trunk neural crest cells (see above figure to determine the approximate location in an embryo) <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> The trunk neural crest coordinates the development of the endocrine system, secretory cells, the peripheral nervous system and, to some degree, skeletal development, as well as innervation of the intestine {{#pmid: 28287247|PMID 28287247}}. The trunk neural cells arise caudally, undergo an epithelial to mesenchymal transition and follow three migratory pathways {{#pmid:20399766|PMID20399766}}.<br /> [[File:Trunk_NCC_migration.jpg|left|450px|thumb|Trunk NCC migration]]<br /> - A dorsolateral pathway (between ectoderm and somites), these become melanocytes, travel up to the point of the dermis and become a major part of the hair follicles and skin <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> - A ventrolateral pathway (through the somites)<br /> - A ventromedial pathway (between neural tube and posterior schlerotome){{#pmid:20399766|PMID20399766}}.<br /> <br /> [[File:Differentiation_of_NCC.jpg|left|580px|thumb|Differentiation of chromaffin cells]]<br /> Migration of neural crest cells from the sympathetic ganglion is what leads to the development of the adrenal medulla. In week 8 of development, immature cells called neuroblasts migrate through to the inner portion of the medulla, where they become the adrenal medulla {{#pmid:19683477|PMID19683477}}. Chromaffin cells are neuroendocrine cells and are found in the sympathetic ganglia and make up the majority of the adrenal medulla{{#pmid:19683477|PMID19683477}}. They synthesise and release a range of hormones in the body and arise from the temporary neural crest. The term chromaffin was inspired by the staining capacity of these cells when they came into contact with chrome salts. They make, store, export and use catecholamines, responsible for making noradrenaline and originate at the caudal region of somites 18-24 of the neural crest, also known as the adrenomedullary region {{#pmid:19683477|PMID19683477}}.<br /> <br /> For cells to leave the neural crest and begin their migration, certain conditions need to be met, that is, the cells need to be loosely connected, their tight junctions becoming relaxed, initiated by "Slug protein" and a loss of N-Cadherin which also leads to the loosening of these junctions. The surrounding matrix as well as chemotactic and stem cell factors of the neural tube are then what dictates how the neural crest cells move, some proteins stopping their migration to that area and others encouraging the movement <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. After splitting apart, the first neural crest cells move ventrally and pass into the spaces between the somites and then, through the anterior portions of each segment until they arrive at the para-aortic sites, where they become the cells of the sympathetic ganglia and the adrenal medulla {{#pmid:19683477|PMID19683477}}. BMP-4 (bone morphogenetic protein 4) then acts on these neural crest cells, preventing them from becoming cells that have a neural function and causing them to become chromaffin cells at the adrenal medulla. Glucocorticoids then play a role in maintenance of chromaffin cells in postnatal life, this was only found recently, as previously it was thought that glucocorticoids were responsible entirely for the differentiation of neural crest cells into chromaffin, or adrenomedullary cells {{#pmid:23220335|PMID23220335}}.<br /> <br /> ===Developmental time course===<br /> ----<br /> <br /> [[File:Adrenal_Medulla_Developmental_Timeline.jpg|right|thumb|500px]]<br /> <br /> The adrenal gland has two distinct sections, the cortex and the medulla, both with different embryonic origins. The cortex accounts for 90% of the adrenal glands and arises from intermediate mesoderm. The medulla only accounts for 10% of the adult adrenal glands, however it has neural crest embryonic origin. The medulla consists of chromaffinoblast cells which are migrant neuroblast cells from the neural crest, therefore the adrenal medulla is a component of the sympathetic nervous system.{{#pmid:21175739|PMID21175739}} Neural crest cells replicate in week 7 and begin to differentiate in week 8, the cells then migrate to the developing adrenal gland in week 9 of development.{{#pmid:25255746|PMID25255746}}{{#pmid:18279781|PMID18279781}} The neural crest cells infiltrate the cortex and the chromaffin cells are scattered islands in the cortex.{{#pmid:23354096|PMID23354096}} Throughout development the cells will become more compact in the centre of the gland, during this period of development the adrenal gland is growing rapidly. The gland is abnormally large until the second trimester and the medulla is much thicker prenatally.{{#pmid:18279781|PMID18279781}}{{#pmid:21175739|PMID21175739}}<br /> <br /> ===Developmental/adult function===<br /> ----<br /> ===Tissue and Organ structure===<br /> <br /> <br /> ====Normal Structure and Function of the Adrenal Medulla====<br /> <br /> The cells of the adrenal medulla are derived from the neural crest as opposed to the mesodermal origins of the cortex. The medulla contains secretory cells called chromaffin cells, due to the agents they produce when oxidised, such as chromate. These cells secrete epinephrine and norepinephrine in response to various substances such as acetylcholine.<br /> <br /> There are three types of cells in the adult adrenal medulla: <br /> 1) Epinephrine cells<br /> <br /> 2) Norepinephrine cells <br /> <br /> 3) Small granule-containing cells (SGCs)<br /> <br /> These cells also produce various other peptides such as substance P and neurotensin. The adrenal medulla also contains presynaptic sympathetic ganglion cells. {{#pmid:1694230|PMID1694230}}<br /> <br /> ====Related Anatomy====<br /> <br /> The tissue and organ structure of the adrenal medulla should be understood with regard to its specialised function within the sympathetic nervous system. <br /> <br /> The medullary region of the adrenal glands is tasked with the endocrine secretions of adrenaline and nor-adrenaline in response to environmental stressors that are signalled for by the sympathetic nervous system. That is, the secretion of fight-or-flight response hormones in order to restrict vasculature to the trunk and increase vascular activity in the peripheral musculature.<br /> <br /> The adrenal glands are supplied by several branches of the great vessels in the abdominal cavity. The secreted catecholamines in the medulla are directly able to pass to the blood stream this way.<br /> <br /> These adrenal glands and their contents are retroperitoneal in the adult and varied in shape, with the left often being semilunar and right being pyramidal. Nervous supply of the adrenal glands is achieved by contributions from the splanchnic nerves of the celiac plexus.<br /> <br /> <br /> ====Role of the Adrenal Medulla====<br /> <br /> Understanding the biochemistry of catecholamines is necessary to see how the adrenal medulla is designed in the stages of embryology and how it is suited for life in the neonate and adult. <br /> <br /> The epinephrine and norepinephrine in the neonate and adult work by primarily changing the osmoregulatory state of vasculature in organs. With the exclusion of their neuromodulatory and neurotransmitter functions, epinephrine and norepinephrine are mainly tasked with the control of sympathetic and parasympathetic supplies. <br /> <br /> Norepinephrine is a constrictor of peripheral vasculature by antagonising the action of surface receptors expressed on the endothelium of blood vessels, specifically Alpha-1 and Alpha-2 receptors, such that vascular resistance increases. <br /> <br /> Epinephrine is both a vasoconstrictor and vasodilator, depending on what receptors it attaches to. As a non-selective adrenergic agonist, it acts on Alpha-1, Alpha-2, Beta-1, Beta-2 and Beta-3 receptors that are found throughout the body's tissues, yielding many different physiological responses.<br /> <br /> <br /> [[File:Dd.jpg|500px|thumb|right|Adult Adrenal Glands in situ]] <br /> ----<br /> <br /> ===Molecular mechanisms/factors/genes===<br /> ----<br /> <br /> ====Genes and Transcription Factors Involved with the Adrenal Medulla's Development====<br /> <br /> Members of the SOX (SRY-Box) gene family have multiple key contributors to Neural Crest in the Adrenal Medulla.<br /> <br /> Mouse models have demonstrated that SOX-10 knock-outs (mice whose DNA has been engineered to not express SOX-10) do not have an adrenal medulla. There has also been suggestion that SOX-8,9 and 10 are all strongly related to the migratory patterning of neural crest cells to the developing adrenal glands.<br /> <br /> The TH gene (for Tyrosine Hydroxylase) encodes the aforementioned enzyme in the adrenal medulla and central nervous system. Tyrosine Hydroxylase is crucial in biochemical pathways and cascades for the synthesis of catecholamines and other CNS neurotransmitters. The conversion from L-Tyrosine to L-DOPA is dependent upon the catalytic action of Tyrosine Hydroxylase. From there, L-DOPA can make Dopamine and eventually Epinephrine and Norepinephrine as well. <br /> <br /> [[File:Catecholamine_Synthesis.jpg|500px|thumb|right|Cascade of Catecholamine Synthesis]]<br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2291442/<br /> https://www.ncbi.nlm.nih.gov/pubmed/19396395<br /> <br /> ===Abnormalities/abnormal development===<br /> ----<br /> ===Animal models===<br /> ----<br /> Animal models are an integral part of research in embryology. In particular due to the moral concerns regarding the use of humans in scientific research. As a result different animals are used as substitutes to simulate the same environments and hope to achieve results that would also be able to represent humans as well. Prenatal adrenal gland development has been described in a number of scientific reports dating from the 1900s to studies in more recent years. These involved a variety of animal models such as ox, sheep, swine and most commonly mice. <br /> <br /> ====Chromaffin cells =(in rat models)====<br /> There has been extensive research conducted into the adrenal chromaffin cells and their embryological developments. As explained above nueral crest cells are pluripotent meaning they are able to differentiate into multiple different cells. The neural crest cells give rise to chromaffin cells of the adrenal medulla.<br /> <br /> To study the formation process of the adrenal medulla in the embryonic period, we visualized chromaffin cells of rat embryos at 13 to 17 days of gestation using anti-tyrosine hydroxylase (TH) antiserum, and created three-dimensional images from serial tissue sections. Between 13 and 15 days of gestation, TH-positive cells (chromaffin cells) migrated from a group of TH-positive cells present dorsal to the adrenal primordium via the medial cranial end of the adrenal primordium into the adrenal primordium. At or after 16 days of gestation, the adrenal capsule was formed except on the ventral aspect of the cranial end of the adrenal gland, from which TH-positive cells penetrated into the adrenal gland.(Pubmed: 15240937) <br /> <br /> Ahonen suggested that some neural crest cells continue migration from the chain ganglia to the lateral sides of aorta, where they form the perirenal ganglia and adrenal medulla, and finally to the ventral side of the aorta to form the preaortic sympathetic tissue. However, that report only showed the several transverse sections of the fetal trunk for the a demonstration of the migration route of neural crest cells. In this study, using three dimensional reconstructed images, we aimed to observe how TH-labeled chromaffin cells penetrate into the adrenal anlage to form the adrenal medulla and whether the migration route of TH - positive cells from the adrenal connects the preaortic sympathetic ganglia <br /> (M.Yamato, R. Yanai, K. Arishima, 2004) <br /> <br /> Prenatal adrenal gland development has been described in numerous published reports covering a wide variety of species, including the ox (Katznelson, 1966; Wrobel and Suss, 1999), sheep (Davies, 1950; Wintour et al., 1975; Upadhyay and Zamboni, 1982; Naaman‐Reperant and Durand, 1997; Grino, 2004), swine (Sokolov et al., 2006) and mouse (Waring, 1935; Ikeda et al., 1994; Sass, 1996; Nyska and Maronpot, 1999; Bland et al., 2003; Val et al., 2007). Adrenal gland development also has been extensively described for humans as well (Kolliker, 1879; Minot, 1892; Zuckerkandl, 1912; Wieman, 1920; Ikeda et al., 1981; Langlois et al., 2002; Hanley and Arit, 2006).<br /> <br /> https://www.sciencedirect.com/science/article/pii/S0925477302004550<br /> http://dev.biologists.org/content/develop/126/13/2935.full.pdf<br /> <br /> ===Current research (labs)===<br /> ----<br /> The findings presented until now have focused on the mechanisms controlling migration along the dorsolateral path. In comparison, our understanding of the mechanisms controlling NCC migration along the ventral path are complicated by the fact that this population comprises multiple precursors that form different derivatives in distinct regions of the embryo. For example, ventrally migrating NCCs either stop within the sclerotome in close association with the neural tube to form neurons and glia of the sensory nervous system (i.e. the dorsal root ganglia [DRG]), while other NCCs continue to migrate further ventrally to form the autonomic nervous system (i.e. sympathetic ganglia and chromaffin cells of the adrenal gland)<br /> <br /> Adrenomedullary chromaffin cells are catecholamine (CA)-producing cells originating from trunk neural crest (NC) via sympathoadrenal progenitors (SAPs). We generated NC and SAPs from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) in vitro via BMP2/FGF2 exposure, ascertained by qPCR and immunoexpression of SOX10, ASCL1, TFAP2α, and PHOX2B, and by fluorescence-activated cell sorting selection for p75NTR and GD2, and confirmed their trunk-like HOX gene expression. We showed that continuing BMP4 and curtailing FGF2 in vitro, augmented with corticosteroid mimetic, induced these cells to upregulate the chromaffin cell-specific marker PNMT and other CA synthesis and storage markers, and we demonstrated noradrenaline and adrenaline by Faglu and high-performance liquid chromatography. We showed these human cells' SAP-like property of migration and differentiation into cells expressing chromaffin cell markers by implanting them into avian embryos in vivo and in chorio-allantoic membrane grafts. These cells have the potential for investigating differentiation of human chromaffin cells and for modeling diseases involving this cell type.<br /> <br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768882/<br /> <br /> ===Glossary===<br /> ----<br /> ===Reference list===</div>

Z5091101 https://embryology.med.unsw.edu.au/embryology/index.php?title=2018_Group_Project_1&diff=356679 2018 Group Project 1 2018-10-10T07:33:16Z

<p>Z5091101: /* Embryonic origins */</p> <hr /> <div>=The Contribution of Neural Crest Cells to the Adrenal Medulla=<br /> ----<br /> {{2018ANAT2341ProjectHeader}}<br /> <br /> <br /> ===Introduction===<br /> [[User:Z5014972|Z5014972]] ([[User talk:Z5014972|talk]]) 12:47, 14 August 2018 (AEST)z5014972 <br /> good review article https://link.springer.com/article/10.1007%2Fs12022-009-9070-6<br /> ----<br /> <br /> <br /> The neural crest of an embryo differentiates and migrates to form various components of the body. One of these tissues is the medulla of the adrenal gland which is involved in the production of adrenalin and noradrenalin. This project will comprehensively outline the history of neural crest research, the embryonic developmental time course, tissue and organ structure, molecular mechanisms, abnormalities, animal models and current research.<br /> <br /> ===History===<br /> ----<br /> '''Describing the neural crest'''<br /> [[File:Wilhelm_His_History_Wilhelm.jpeg|left|230px|thumb|Wilhelm His]]<br /> The "neural crest" is a structure in the embryo and is the junction between the neural and epidermal ectoderm. It is exclusive to vertebrates and forms a range of structures{{#pmid:22230617|PMID22230617}}. The neural crest contributes a large number of cells of varying structure and function that directly or indirectly contribute to the development of tissues and organs within the body {{#pmid:19179766|PMID19179766}}. In 1868, the neural crest cells were first identified in a chick embryo as a collection of cells known as "Zwischenstrang" by Professor Wilhelm His {{#pmid:22820859|PMID22820859}}. Wilhelm His was among the first to provide an explanation for the mechanics governing the developing embryo as well as the physiology and the organs that the differing germinal regions would eventually give rise to. In 1878, the term neural ridge was used to describe this collection of cells but the term neural crest was later coined by Arthur Milnes Marshall in 1879 in a paper he worked on disseminating the knowledge from his research on the development of cranial nerves in chicken embryos. {{#pmid:19179766|PMID19179766}}.<br /> [[File:NC Location.jpg|left|450px|thumb|The neural crest]]<br /> <br /> '''1890s-1950s'''<br /> The neural crest is the point of origin for spinal/cranial ganglia and neurons. This theory received little criticism and was not contested much by other researchers prior to the 1890s. This is owing to the fact that the neural crest is quite closely related to the neural tube and thus this relationship makes sense. This discovery was made by His and Marshall, however, they found this out independently of one another.In the 1890s, Julia Platt, claimed that odontoblasts as well as the cartilages forming the facial and pharyngeal arch skeletons came from the ectoderm. This created much debate and was contested by many{{#pmid:22820859|PMID22820859}}. <br /> <br /> This is because this theory completely contradicted the germ-layer theory, whereby skeletal tissues originate at the mesoderm and not the ectoderm. The controversies this finding created brought about a slowing down of research, as demonstrated by a gap of almost 40 years between the theory that skeletal tissues originating from the neural crest. Today, it is known that the neural crest does indeed play a role in the development of the skeleton in vertebrates, particularly, the cranial neural crest. Although these studies were occurring, the focus was still primarily on researching pigment cells and ganglia of the spine up until the 1950s, when Sven Hörstadius' major work on the neural crest was published, titled "The Neural Crest: Its properties and derivatives in the light of experimental research". This work focused on experimental data tracing the development of the cartilaginous skeleton derived from the neural crest {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1960s - 1970s'''<br /> In the 1960s, the migration patterns of neural crest cells were studied in avian embryos (birds). This was a shift from studying the embryos of amphibians. This was inspired by studies conducted in the 1960s on neural crest cells migrating from the brain and spinal cord, known as trunk and cranial neural crest cells {{#pmid:19179766|PMID19179766}}. The cranial neural crest eventually becomes the bones, cartilage and connective tissues forming the foundation of the face, ears and teeth. The trunk neural crest cells can either become melanocytes or can migrate into sclerotomes which are later contributors to the cartilage of the spine and the dorsal root ganglia {{#pmid:22820859|PMID22820859}}. The cells in the trunk neural crest that migrate vertically become the sympathetic ganglia, the nerves proximal to the aorta and the adrenal medulla <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. In the 1970s many detailed maps signifying the pathways of many of the neural crest cells appeared as well as an understanding that the environment in which the neural crest cells are found plays a major role in their final development as well as the occurrences of abnormalities in the fetus {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1980s - 21st century'''<br /> [[File:Regions_of_NC_Cells.jpg|left|Neural crest regions|thumb]]<br /> From the 1980s-1990s, the causative agent of organ transformation from one to another (homeotic patterning), as well as the Hox genes which regulate the axis of most symmetrical animal embryos were founded and studied. The neural crest, which previously was divided into the cranial and trunk regions, was now further divided into the vagal and sacral neural crest, the cardiac neural crest and the cephalic neural crest {{#pmid:19179766|PMID19179766}}. The vagal & sacral neural crest gives rise to the parasympathetic ganglia found in the gut. Without these ganglia, peristalsis, is not possible <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. The cardiac neural crest contributes to the valves, septa and major blood vessels of the heart, as well as connective tissues and cartilage{{#pmid:19179766|PMID19179766}}. This is important for the structure of the heart as well as its overall function, enabling it to move blood around the body efficiently as well as keep pulmonary and aortic circulation separated <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> <br /> <br /> Today, knowledge of the neural crest cells, their migration patterns, modes of differentiation, derivatives and apoptosis (cell death) are being studied extensively. This is being done on a comparative basis between different organisms, to add further evidence for evolution {{#pmid:19179766|PMID19179766}}. The neural crest is definitely forging a "crest" between the fields of developmental and evolutionary biology, as it is a structure '''shared exclusively by all vertebrates'''. Invertebrates do not derive their specialised cells from the neural crest as they do not have one, rather, they derive these from the endomesoderm {{#pmid:22230617|PMID22230617}}.<br /> <br /> '''Future directions'''<br /> <br /> Since its discovery by His, the neural crest field has made great progress, from studies performed on the structure, to analysis of the molecules and whether certain aspects of the neural crest are specific to a single species of organism, or to all vertebrates collectively. Future work on the cranial neural crest needs to be done as well as identifying and categorising the networks responsible for the proliferation and death of cells, as well as how the cells move and migrate, as well as the gene regulatory networks (GRNs) that regulate the synthesis of proteins. Advances in technology will undeniable lead us to more answers on the subject {{#pmid:22230617|PMID22230617}}.<br /> <br /> ===Embryonic origins===<br /> ----<br /> <br /> The adrenal gland is made up of the adrenal cortex and adrenal medulla, which both have different embryonic origins. The adrenal medulla arises from the neural crest tissue, found near the level of the coeliac plexus & sympathetic ganglion at somites 18-24 {{#pmid:16124976|PMID16124976}}. Specifically, this neural crest tissue comes from the trunk neural crest cells (see above figure to determine the approximate location in an embryo) <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> The trunk neural crest coordinates the development of the endocrine system, secretory cells, the peripheral nervous system and, to some degree, skeletal development, as well as innervation of the intestine {{#pmid: 28287247|PMID 28287247}}. The trunk neural cells arise caudally, undergo an epithelial to mesenchymal transition and follow three migratory pathways {{#pmid:20399766|PMID20399766}}.<br /> <br /> - A dorsolateral pathway (between ectoderm and somites), these become melanocytes, travel up to the point of the dermis and become a major part of the hair follicles and skin <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> - A ventrolateral pathway (through the somites)<br /> - A ventromedial pathway (between neural tube and posterior schlerotome){{#pmid:20399766|PMID20399766}}.<br /> <br /> Migration of neural crest cells from the sympathetic ganglion is what leads to the development of the adrenal medulla. In week 8 of development, immature cells called neuroblasts migrate through to the inner portion of the medulla, where they become the adrenal medulla {{#pmid:19683477|PMID19683477}}. Chromaffin cells are neuroendocrine cells and are found in the sympathetic ganglia and make up the majority of the adrenal medulla{{#pmid:19683477|PMID19683477}}. They synthesise and release a range of hormones in the body and arise from the temporary neural crest. The term chromaffin was inspired by the staining capacity of these cells when they came into contact with chrome salts. They make, store, export and use catecholamines, responsible for making noradrenaline and originate at the caudal region of somites 18-24 of the neural crest, also known as the adrenomedullary region {{#pmid:19683477|PMID19683477}}.<br /> [[File:Trunk_NCC_migration.jpg|left|450px|thumb|Trunk NCC migration]]<br /> <br /> For cells to leave the neural crest and begin their migration, certain conditions need to be met, that is, the cells need to be loosely connected, their tight junctions becoming relaxed, initiated by "Slug protein" and a loss of N-Cadherin which also leads to the loosening of these junctions. The surrounding matrix as well as chemotactic and stem cell factors of the neural tube are then what dictates how the neural crest cells move, some proteins stopping their migration to that area and others encouraging the movement <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. After splitting apart, the first neural crest cells move ventrally and pass into the spaces between the somites and then, through the anterior portions of each segment until they arrive at the para-aortic sites, where they become the cells of the sympathetic ganglia and the adrenal medulla {{#pmid:19683477|PMID19683477}}. BMP-4 (bone morphogenetic protein 4) then acts on these neural crest cells, preventing them from becoming cells that have a neural function and causing them to become chromaffin cells at the adrenal medulla. Glucocorticoids then play a role in maintenance of chromaffin cells in postnatal life, this was only found recently, as previously it was thought that glucocorticoids were responsible entirely for the differentiation of neural crest cells into chromaffin, or adrenomedullary cells {{#pmid:23220335|PMID23220335}}.<br /> <br /> [[File:Differentiation_of_NCC.jpg|left|580px|thumb|Differentiation of chromaffin cells]]<br /> <br /> ===Developmental time course===<br /> ----<br /> <br /> [[File:Adrenal_Medulla_Developmental_Timeline.jpg|right|thumb|500px]]<br /> <br /> The adrenal gland has two distinct sections, the cortex and the medulla, both with different embryonic origins. The cortex accounts for 90% of the adrenal glands and arises from intermediate mesoderm. The medulla only accounts for 10% of the adult adrenal glands, however it has neural crest embryonic origin. The medulla consists of chromaffinoblast cells which are migrant neuroblast cells from the neural crest, therefore the adrenal medulla is a component of the sympathetic nervous system.{{#pmid:21175739|PMID21175739}} Neural crest cells replicate in week 7 and begin to differentiate in week 8, the cells then migrate to the developing adrenal gland in week 9 of development.{{#pmid:25255746|PMID25255746}}{{#pmid:18279781|PMID18279781}} The neural crest cells infiltrate the cortex and the chromaffin cells are scattered islands in the cortex.{{#pmid:23354096|PMID23354096}} Throughout development the cells will become more compact in the centre of the gland, during this period of development the adrenal gland is growing rapidly. The gland is abnormally large until the second trimester and the medulla is much thicker prenatally.{{#pmid:18279781|PMID18279781}}{{#pmid:21175739|PMID21175739}}<br /> <br /> ===Developmental/adult function===<br /> ----<br /> ===Tissue and Organ structure===<br /> <br /> <br /> ====Normal Structure and Function of the Adrenal Medulla====<br /> <br /> The cells of the adrenal medulla are derived from the neural crest as opposed to the mesodermal origins of the cortex. The medulla contains secretory cells called chromaffin cells, due to the agents they produce when oxidised, such as chromate. These cells secrete epinephrine and norepinephrine in response to various substances such as acetylcholine.<br /> <br /> There are three types of cells in the adult adrenal medulla: <br /> 1) Epinephrine cells<br /> <br /> 2) Norepinephrine cells <br /> <br /> 3) Small granule-containing cells (SGCs)<br /> <br /> These cells also produce various other peptides such as substance P and neurotensin. The adrenal medulla also contains presynaptic sympathetic ganglion cells. {{#pmid:1694230|PMID1694230}}<br /> <br /> ====Related Anatomy====<br /> <br /> The tissue and organ structure of the adrenal medulla should be understood with regard to its specialised function within the sympathetic nervous system. <br /> <br /> The medullary region of the adrenal glands is tasked with the endocrine secretions of adrenaline and nor-adrenaline in response to environmental stressors that are signalled for by the sympathetic nervous system. That is, the secretion of fight-or-flight response hormones in order to restrict vasculature to the trunk and increase vascular activity in the peripheral musculature.<br /> <br /> The adrenal glands are supplied by several branches of the great vessels in the abdominal cavity. The secreted catecholamines in the medulla are directly able to pass to the blood stream this way.<br /> <br /> These adrenal glands and their contents are retroperitoneal in the adult and varied in shape, with the left often being semilunar and right being pyramidal. Nervous supply of the adrenal glands is achieved by contributions from the splanchnic nerves of the celiac plexus.<br /> <br /> <br /> ====Role of the Adrenal Medulla====<br /> <br /> Understanding the biochemistry of catecholamines is necessary to see how the adrenal medulla is designed in the stages of embryology and how it is suited for life in the neonate and adult. <br /> <br /> The epinephrine and norepinephrine in the neonate and adult work by primarily changing the osmoregulatory state of vasculature in organs. With the exclusion of their neuromodulatory and neurotransmitter functions, epinephrine and norepinephrine are mainly tasked with the control of sympathetic and parasympathetic supplies. <br /> <br /> Norepinephrine is a constrictor of peripheral vasculature by antagonising the action of surface receptors expressed on the endothelium of blood vessels, specifically Alpha-1 and Alpha-2 receptors, such that vascular resistance increases. <br /> <br /> Epinephrine is both a vasoconstrictor and vasodilator, depending on what receptors it attaches to. As a non-selective adrenergic agonist, it acts on Alpha-1, Alpha-2, Beta-1, Beta-2 and Beta-3 receptors that are found throughout the body's tissues, yielding many different physiological responses.<br /> <br /> <br /> [[File:Dd.jpg|500px|thumb|right|Adult Adrenal Glands in situ]] <br /> ----<br /> <br /> ===Molecular mechanisms/factors/genes===<br /> ----<br /> <br /> ====Genes and Transcription Factors Involved with the Adrenal Medulla's Development====<br /> <br /> Members of the SOX (SRY-Box) gene family have multiple key contributors to Neural Crest in the Adrenal Medulla.<br /> <br /> Mouse models have demonstrated that SOX-10 knock-outs (mice whose DNA has been engineered to not express SOX-10) do not have an adrenal medulla. There has also been suggestion that SOX-8,9 and 10 are all strongly related to the migratory patterning of neural crest cells to the developing adrenal glands.<br /> <br /> The TH gene (for Tyrosine Hydroxylase) encodes the aforementioned enzyme in the adrenal medulla and central nervous system. Tyrosine Hydroxylase is crucial in biochemical pathways and cascades for the synthesis of catecholamines and other CNS neurotransmitters. The conversion from L-Tyrosine to L-DOPA is dependent upon the catalytic action of Tyrosine Hydroxylase. From there, L-DOPA can make Dopamine and eventually Epinephrine and Norepinephrine as well. <br /> <br /> [[File:Catecholamine_Synthesis.jpg|500px|thumb|right|Cascade of Catecholamine Synthesis]]<br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2291442/<br /> https://www.ncbi.nlm.nih.gov/pubmed/19396395<br /> <br /> ===Abnormalities/abnormal development===<br /> ----<br /> ===Animal models===<br /> ----<br /> Animal models are an integral part of research in embryology. In particular due to the moral concerns regarding the use of humans in scientific research. As a result different animals are used as substitutes to simulate the same environments and hope to achieve results that would also be able to represent humans as well. Prenatal adrenal gland development has been described in a number of scientific reports dating from the 1900s to studies in more recent years. These involved a variety of animal models such as ox, sheep, swine and most commonly mice. <br /> <br /> ====Chromaffin cells =(in rat models)====<br /> There has been extensive research conducted into the adrenal chromaffin cells and their embryological developments. As explained above nueral crest cells are pluripotent meaning they are able to differentiate into multiple different cells. The neural crest cells give rise to chromaffin cells of the adrenal medulla.<br /> <br /> To study the formation process of the adrenal medulla in the embryonic period, we visualized chromaffin cells of rat embryos at 13 to 17 days of gestation using anti-tyrosine hydroxylase (TH) antiserum, and created three-dimensional images from serial tissue sections. Between 13 and 15 days of gestation, TH-positive cells (chromaffin cells) migrated from a group of TH-positive cells present dorsal to the adrenal primordium via the medial cranial end of the adrenal primordium into the adrenal primordium. At or after 16 days of gestation, the adrenal capsule was formed except on the ventral aspect of the cranial end of the adrenal gland, from which TH-positive cells penetrated into the adrenal gland.(Pubmed: 15240937) <br /> <br /> Ahonen suggested that some neural crest cells continue migration from the chain ganglia to the lateral sides of aorta, where they form the perirenal ganglia and adrenal medulla, and finally to the ventral side of the aorta to form the preaortic sympathetic tissue. However, that report only showed the several transverse sections of the fetal trunk for the a demonstration of the migration route of neural crest cells. In this study, using three dimensional reconstructed images, we aimed to observe how TH-labeled chromaffin cells penetrate into the adrenal anlage to form the adrenal medulla and whether the migration route of TH - positive cells from the adrenal connects the preaortic sympathetic ganglia <br /> (M.Yamato, R. Yanai, K. Arishima, 2004) <br /> <br /> Prenatal adrenal gland development has been described in numerous published reports covering a wide variety of species, including the ox (Katznelson, 1966; Wrobel and Suss, 1999), sheep (Davies, 1950; Wintour et al., 1975; Upadhyay and Zamboni, 1982; Naaman‐Reperant and Durand, 1997; Grino, 2004), swine (Sokolov et al., 2006) and mouse (Waring, 1935; Ikeda et al., 1994; Sass, 1996; Nyska and Maronpot, 1999; Bland et al., 2003; Val et al., 2007). Adrenal gland development also has been extensively described for humans as well (Kolliker, 1879; Minot, 1892; Zuckerkandl, 1912; Wieman, 1920; Ikeda et al., 1981; Langlois et al., 2002; Hanley and Arit, 2006).<br /> <br /> https://www.sciencedirect.com/science/article/pii/S0925477302004550<br /> http://dev.biologists.org/content/develop/126/13/2935.full.pdf<br /> <br /> ===Current research (labs)===<br /> ----<br /> The findings presented until now have focused on the mechanisms controlling migration along the dorsolateral path. In comparison, our understanding of the mechanisms controlling NCC migration along the ventral path are complicated by the fact that this population comprises multiple precursors that form different derivatives in distinct regions of the embryo. For example, ventrally migrating NCCs either stop within the sclerotome in close association with the neural tube to form neurons and glia of the sensory nervous system (i.e. the dorsal root ganglia [DRG]), while other NCCs continue to migrate further ventrally to form the autonomic nervous system (i.e. sympathetic ganglia and chromaffin cells of the adrenal gland)<br /> <br /> Adrenomedullary chromaffin cells are catecholamine (CA)-producing cells originating from trunk neural crest (NC) via sympathoadrenal progenitors (SAPs). We generated NC and SAPs from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) in vitro via BMP2/FGF2 exposure, ascertained by qPCR and immunoexpression of SOX10, ASCL1, TFAP2α, and PHOX2B, and by fluorescence-activated cell sorting selection for p75NTR and GD2, and confirmed their trunk-like HOX gene expression. We showed that continuing BMP4 and curtailing FGF2 in vitro, augmented with corticosteroid mimetic, induced these cells to upregulate the chromaffin cell-specific marker PNMT and other CA synthesis and storage markers, and we demonstrated noradrenaline and adrenaline by Faglu and high-performance liquid chromatography. We showed these human cells' SAP-like property of migration and differentiation into cells expressing chromaffin cell markers by implanting them into avian embryos in vivo and in chorio-allantoic membrane grafts. These cells have the potential for investigating differentiation of human chromaffin cells and for modeling diseases involving this cell type.<br /> <br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768882/<br /> <br /> ===Glossary===<br /> ----<br /> ===Reference list===</div>

Z5091101 https://embryology.med.unsw.edu.au/embryology/index.php?title=2018_Group_Project_1&diff=356677 2018 Group Project 1 2018-10-10T07:32:43Z

<p>Z5091101: /* Embryonic origins */</p> <hr /> <div>=The Contribution of Neural Crest Cells to the Adrenal Medulla=<br /> ----<br /> {{2018ANAT2341ProjectHeader}}<br /> <br /> <br /> ===Introduction===<br /> [[User:Z5014972|Z5014972]] ([[User talk:Z5014972|talk]]) 12:47, 14 August 2018 (AEST)z5014972 <br /> good review article https://link.springer.com/article/10.1007%2Fs12022-009-9070-6<br /> ----<br /> <br /> <br /> The neural crest of an embryo differentiates and migrates to form various components of the body. One of these tissues is the medulla of the adrenal gland which is involved in the production of adrenalin and noradrenalin. This project will comprehensively outline the history of neural crest research, the embryonic developmental time course, tissue and organ structure, molecular mechanisms, abnormalities, animal models and current research.<br /> <br /> ===History===<br /> ----<br /> '''Describing the neural crest'''<br /> [[File:Wilhelm_His_History_Wilhelm.jpeg|left|230px|thumb|Wilhelm His]]<br /> The "neural crest" is a structure in the embryo and is the junction between the neural and epidermal ectoderm. It is exclusive to vertebrates and forms a range of structures{{#pmid:22230617|PMID22230617}}. The neural crest contributes a large number of cells of varying structure and function that directly or indirectly contribute to the development of tissues and organs within the body {{#pmid:19179766|PMID19179766}}. In 1868, the neural crest cells were first identified in a chick embryo as a collection of cells known as "Zwischenstrang" by Professor Wilhelm His {{#pmid:22820859|PMID22820859}}. Wilhelm His was among the first to provide an explanation for the mechanics governing the developing embryo as well as the physiology and the organs that the differing germinal regions would eventually give rise to. In 1878, the term neural ridge was used to describe this collection of cells but the term neural crest was later coined by Arthur Milnes Marshall in 1879 in a paper he worked on disseminating the knowledge from his research on the development of cranial nerves in chicken embryos. {{#pmid:19179766|PMID19179766}}.<br /> [[File:NC Location.jpg|left|450px|thumb|The neural crest]]<br /> <br /> '''1890s-1950s'''<br /> The neural crest is the point of origin for spinal/cranial ganglia and neurons. This theory received little criticism and was not contested much by other researchers prior to the 1890s. This is owing to the fact that the neural crest is quite closely related to the neural tube and thus this relationship makes sense. This discovery was made by His and Marshall, however, they found this out independently of one another.In the 1890s, Julia Platt, claimed that odontoblasts as well as the cartilages forming the facial and pharyngeal arch skeletons came from the ectoderm. This created much debate and was contested by many{{#pmid:22820859|PMID22820859}}. <br /> <br /> This is because this theory completely contradicted the germ-layer theory, whereby skeletal tissues originate at the mesoderm and not the ectoderm. The controversies this finding created brought about a slowing down of research, as demonstrated by a gap of almost 40 years between the theory that skeletal tissues originating from the neural crest. Today, it is known that the neural crest does indeed play a role in the development of the skeleton in vertebrates, particularly, the cranial neural crest. Although these studies were occurring, the focus was still primarily on researching pigment cells and ganglia of the spine up until the 1950s, when Sven Hörstadius' major work on the neural crest was published, titled "The Neural Crest: Its properties and derivatives in the light of experimental research". This work focused on experimental data tracing the development of the cartilaginous skeleton derived from the neural crest {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1960s - 1970s'''<br /> In the 1960s, the migration patterns of neural crest cells were studied in avian embryos (birds). This was a shift from studying the embryos of amphibians. This was inspired by studies conducted in the 1960s on neural crest cells migrating from the brain and spinal cord, known as trunk and cranial neural crest cells {{#pmid:19179766|PMID19179766}}. The cranial neural crest eventually becomes the bones, cartilage and connective tissues forming the foundation of the face, ears and teeth. The trunk neural crest cells can either become melanocytes or can migrate into sclerotomes which are later contributors to the cartilage of the spine and the dorsal root ganglia {{#pmid:22820859|PMID22820859}}. The cells in the trunk neural crest that migrate vertically become the sympathetic ganglia, the nerves proximal to the aorta and the adrenal medulla <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. In the 1970s many detailed maps signifying the pathways of many of the neural crest cells appeared as well as an understanding that the environment in which the neural crest cells are found plays a major role in their final development as well as the occurrences of abnormalities in the fetus {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1980s - 21st century'''<br /> [[File:Regions_of_NC_Cells.jpg|left|Neural crest regions|thumb]]<br /> From the 1980s-1990s, the causative agent of organ transformation from one to another (homeotic patterning), as well as the Hox genes which regulate the axis of most symmetrical animal embryos were founded and studied. The neural crest, which previously was divided into the cranial and trunk regions, was now further divided into the vagal and sacral neural crest, the cardiac neural crest and the cephalic neural crest {{#pmid:19179766|PMID19179766}}. The vagal & sacral neural crest gives rise to the parasympathetic ganglia found in the gut. Without these ganglia, peristalsis, is not possible <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. The cardiac neural crest contributes to the valves, septa and major blood vessels of the heart, as well as connective tissues and cartilage{{#pmid:19179766|PMID19179766}}. This is important for the structure of the heart as well as its overall function, enabling it to move blood around the body efficiently as well as keep pulmonary and aortic circulation separated <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> <br /> <br /> Today, knowledge of the neural crest cells, their migration patterns, modes of differentiation, derivatives and apoptosis (cell death) are being studied extensively. This is being done on a comparative basis between different organisms, to add further evidence for evolution {{#pmid:19179766|PMID19179766}}. The neural crest is definitely forging a "crest" between the fields of developmental and evolutionary biology, as it is a structure '''shared exclusively by all vertebrates'''. Invertebrates do not derive their specialised cells from the neural crest as they do not have one, rather, they derive these from the endomesoderm {{#pmid:22230617|PMID22230617}}.<br /> <br /> '''Future directions'''<br /> <br /> Since its discovery by His, the neural crest field has made great progress, from studies performed on the structure, to analysis of the molecules and whether certain aspects of the neural crest are specific to a single species of organism, or to all vertebrates collectively. Future work on the cranial neural crest needs to be done as well as identifying and categorising the networks responsible for the proliferation and death of cells, as well as how the cells move and migrate, as well as the gene regulatory networks (GRNs) that regulate the synthesis of proteins. Advances in technology will undeniable lead us to more answers on the subject {{#pmid:22230617|PMID22230617}}.<br /> <br /> ===Embryonic origins===<br /> ----<br /> <br /> The adrenal gland is made up of the adrenal cortex and adrenal medulla, which both have different embryonic origins. The adrenal medulla arises from the neural crest tissue, found near the level of the coeliac plexus & sympathetic ganglion at somites 18-24 {{#pmid:16124976|PMID16124976}}. Specifically, this neural crest tissue comes from the trunk neural crest cells (see above figure to determine the approximate location in an embryo) <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> The trunk neural crest coordinates the development of the endocrine system, secretory cells, the peripheral nervous system and, to some degree, skeletal development, as well as innervation of the intestine {{#pmid: 28287247|PMID 28287247}}. The trunk neural cells arise caudally, undergo an epithelial to mesenchymal transition and follow three migratory pathways {{#pmid:20399766|PMID20399766}}.<br /> <br /> - A dorsolateral pathway (between ectoderm and somites), these become melanocytes, travel up to the point of the dermis and become a major part of the hair follicles and skin <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> - A ventrolateral pathway (through the somites)<br /> - A ventromedial pathway (between neural tube and posterior schlerotome){{#pmid:20399766|PMID20399766}}.<br /> <br /> Migration of neural crest cells from the sympathetic ganglion is what leads to the development of the adrenal medulla. In week 8 of development, immature cells called neuroblasts migrate through to the inner portion of the medulla, where they become the adrenal medulla {{#pmid:19683477|PMID19683477}}. Chromaffin cells are neuroendocrine cells and are found in the sympathetic ganglia and make up the majority of the adrenal medulla{{#pmid:19683477|PMID19683477}}. They synthesise and release a range of hormones in the body and arise from the temporary neural crest. The term chromaffin was inspired by the staining capacity of these cells when they came into contact with chrome salts. They make, store, export and use catecholamines, responsible for making noradrenaline and originate at the caudal region of somites 18-24 of the neural crest, also known as the adrenomedullary region {{#pmid:19683477|PMID19683477}}.<br /> [[File:Trunk_NCC_migration.jpg|left|450px|thumb|Trunk NCC migration]]<br /> <br /> For cells to leave the neural crest and begin their migration, certain conditions need to be met, that is, the cells need to be loosely connected, their tight junctions becoming relaxed, initiated by "Slug protein" and a loss of N-Cadherin which also leads to the loosening of these junctions. The surrounding matrix as well as chemotactic and stem cell factors of the neural tube are then what dictates how the neural crest cells move, some proteins stopping their migration to that area and others encouraging the movement <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. After splitting apart, the first neural crest cells move ventrally and pass into the spaces between the somites and then, through the anterior portions of each segment until they arrive at the para-aortic sites, where they become the cells of the sympathetic ganglia and the adrenal medulla {{#pmid:19683477|PMID19683477}}. BMP-4 (bone morphogenetic protein 4) then acts on these neural crest cells, preventing them from becoming cells that have a neural function and causing them to become chromaffin cells at the adrenal medulla. Glucocorticoids then play a role in maintenance of chromaffin cells in postnatal life, this was only found recently, as previously it was thought that glucocorticoids were responsible entirely for the differentiation of neural crest cells into chromaffin, or adrenomedullary cells {{#pmid:23220335|PMID23220335}}.<br /> <br /> [[File:Differentiation_of_NCC.jpg|lefy|450px|thumb|Differentiation of chromaffin cells]]<br /> <br /> ===Developmental time course===<br /> ----<br /> <br /> [[File:Adrenal_Medulla_Developmental_Timeline.jpg|right|thumb|500px]]<br /> <br /> The adrenal gland has two distinct sections, the cortex and the medulla, both with different embryonic origins. The cortex accounts for 90% of the adrenal glands and arises from intermediate mesoderm. The medulla only accounts for 10% of the adult adrenal glands, however it has neural crest embryonic origin. The medulla consists of chromaffinoblast cells which are migrant neuroblast cells from the neural crest, therefore the adrenal medulla is a component of the sympathetic nervous system.{{#pmid:21175739|PMID21175739}} Neural crest cells replicate in week 7 and begin to differentiate in week 8, the cells then migrate to the developing adrenal gland in week 9 of development.{{#pmid:25255746|PMID25255746}}{{#pmid:18279781|PMID18279781}} The neural crest cells infiltrate the cortex and the chromaffin cells are scattered islands in the cortex.{{#pmid:23354096|PMID23354096}} Throughout development the cells will become more compact in the centre of the gland, during this period of development the adrenal gland is growing rapidly. The gland is abnormally large until the second trimester and the medulla is much thicker prenatally.{{#pmid:18279781|PMID18279781}}{{#pmid:21175739|PMID21175739}}<br /> <br /> ===Developmental/adult function===<br /> ----<br /> ===Tissue and Organ structure===<br /> <br /> <br /> ====Normal Structure and Function of the Adrenal Medulla====<br /> <br /> The cells of the adrenal medulla are derived from the neural crest as opposed to the mesodermal origins of the cortex. The medulla contains secretory cells called chromaffin cells, due to the agents they produce when oxidised, such as chromate. These cells secrete epinephrine and norepinephrine in response to various substances such as acetylcholine.<br /> <br /> There are three types of cells in the adult adrenal medulla: <br /> 1) Epinephrine cells<br /> <br /> 2) Norepinephrine cells <br /> <br /> 3) Small granule-containing cells (SGCs)<br /> <br /> These cells also produce various other peptides such as substance P and neurotensin. The adrenal medulla also contains presynaptic sympathetic ganglion cells. {{#pmid:1694230|PMID1694230}}<br /> <br /> ====Related Anatomy====<br /> <br /> The tissue and organ structure of the adrenal medulla should be understood with regard to its specialised function within the sympathetic nervous system. <br /> <br /> The medullary region of the adrenal glands is tasked with the endocrine secretions of adrenaline and nor-adrenaline in response to environmental stressors that are signalled for by the sympathetic nervous system. That is, the secretion of fight-or-flight response hormones in order to restrict vasculature to the trunk and increase vascular activity in the peripheral musculature.<br /> <br /> The adrenal glands are supplied by several branches of the great vessels in the abdominal cavity. The secreted catecholamines in the medulla are directly able to pass to the blood stream this way.<br /> <br /> These adrenal glands and their contents are retroperitoneal in the adult and varied in shape, with the left often being semilunar and right being pyramidal. Nervous supply of the adrenal glands is achieved by contributions from the splanchnic nerves of the celiac plexus.<br /> <br /> <br /> ====Role of the Adrenal Medulla====<br /> <br /> Understanding the biochemistry of catecholamines is necessary to see how the adrenal medulla is designed in the stages of embryology and how it is suited for life in the neonate and adult. <br /> <br /> The epinephrine and norepinephrine in the neonate and adult work by primarily changing the osmoregulatory state of vasculature in organs. With the exclusion of their neuromodulatory and neurotransmitter functions, epinephrine and norepinephrine are mainly tasked with the control of sympathetic and parasympathetic supplies. <br /> <br /> Norepinephrine is a constrictor of peripheral vasculature by antagonising the action of surface receptors expressed on the endothelium of blood vessels, specifically Alpha-1 and Alpha-2 receptors, such that vascular resistance increases. <br /> <br /> Epinephrine is both a vasoconstrictor and vasodilator, depending on what receptors it attaches to. As a non-selective adrenergic agonist, it acts on Alpha-1, Alpha-2, Beta-1, Beta-2 and Beta-3 receptors that are found throughout the body's tissues, yielding many different physiological responses.<br /> <br /> <br /> [[File:Dd.jpg|500px|thumb|right|Adult Adrenal Glands in situ]] <br /> ----<br /> <br /> ===Molecular mechanisms/factors/genes===<br /> ----<br /> <br /> ====Genes and Transcription Factors Involved with the Adrenal Medulla's Development====<br /> <br /> Members of the SOX (SRY-Box) gene family have multiple key contributors to Neural Crest in the Adrenal Medulla.<br /> <br /> Mouse models have demonstrated that SOX-10 knock-outs (mice whose DNA has been engineered to not express SOX-10) do not have an adrenal medulla. There has also been suggestion that SOX-8,9 and 10 are all strongly related to the migratory patterning of neural crest cells to the developing adrenal glands.<br /> <br /> The TH gene (for Tyrosine Hydroxylase) encodes the aforementioned enzyme in the adrenal medulla and central nervous system. Tyrosine Hydroxylase is crucial in biochemical pathways and cascades for the synthesis of catecholamines and other CNS neurotransmitters. The conversion from L-Tyrosine to L-DOPA is dependent upon the catalytic action of Tyrosine Hydroxylase. From there, L-DOPA can make Dopamine and eventually Epinephrine and Norepinephrine as well. <br /> <br /> [[File:Catecholamine_Synthesis.jpg|500px|thumb|right|Cascade of Catecholamine Synthesis]]<br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2291442/<br /> https://www.ncbi.nlm.nih.gov/pubmed/19396395<br /> <br /> ===Abnormalities/abnormal development===<br /> ----<br /> ===Animal models===<br /> ----<br /> Animal models are an integral part of research in embryology. In particular due to the moral concerns regarding the use of humans in scientific research. As a result different animals are used as substitutes to simulate the same environments and hope to achieve results that would also be able to represent humans as well. Prenatal adrenal gland development has been described in a number of scientific reports dating from the 1900s to studies in more recent years. These involved a variety of animal models such as ox, sheep, swine and most commonly mice. <br /> <br /> ====Chromaffin cells =(in rat models)====<br /> There has been extensive research conducted into the adrenal chromaffin cells and their embryological developments. As explained above nueral crest cells are pluripotent meaning they are able to differentiate into multiple different cells. The neural crest cells give rise to chromaffin cells of the adrenal medulla.<br /> <br /> To study the formation process of the adrenal medulla in the embryonic period, we visualized chromaffin cells of rat embryos at 13 to 17 days of gestation using anti-tyrosine hydroxylase (TH) antiserum, and created three-dimensional images from serial tissue sections. Between 13 and 15 days of gestation, TH-positive cells (chromaffin cells) migrated from a group of TH-positive cells present dorsal to the adrenal primordium via the medial cranial end of the adrenal primordium into the adrenal primordium. At or after 16 days of gestation, the adrenal capsule was formed except on the ventral aspect of the cranial end of the adrenal gland, from which TH-positive cells penetrated into the adrenal gland.(Pubmed: 15240937) <br /> <br /> Ahonen suggested that some neural crest cells continue migration from the chain ganglia to the lateral sides of aorta, where they form the perirenal ganglia and adrenal medulla, and finally to the ventral side of the aorta to form the preaortic sympathetic tissue. However, that report only showed the several transverse sections of the fetal trunk for the a demonstration of the migration route of neural crest cells. In this study, using three dimensional reconstructed images, we aimed to observe how TH-labeled chromaffin cells penetrate into the adrenal anlage to form the adrenal medulla and whether the migration route of TH - positive cells from the adrenal connects the preaortic sympathetic ganglia <br /> (M.Yamato, R. Yanai, K. Arishima, 2004) <br /> <br /> Prenatal adrenal gland development has been described in numerous published reports covering a wide variety of species, including the ox (Katznelson, 1966; Wrobel and Suss, 1999), sheep (Davies, 1950; Wintour et al., 1975; Upadhyay and Zamboni, 1982; Naaman‐Reperant and Durand, 1997; Grino, 2004), swine (Sokolov et al., 2006) and mouse (Waring, 1935; Ikeda et al., 1994; Sass, 1996; Nyska and Maronpot, 1999; Bland et al., 2003; Val et al., 2007). Adrenal gland development also has been extensively described for humans as well (Kolliker, 1879; Minot, 1892; Zuckerkandl, 1912; Wieman, 1920; Ikeda et al., 1981; Langlois et al., 2002; Hanley and Arit, 2006).<br /> <br /> https://www.sciencedirect.com/science/article/pii/S0925477302004550<br /> http://dev.biologists.org/content/develop/126/13/2935.full.pdf<br /> <br /> ===Current research (labs)===<br /> ----<br /> The findings presented until now have focused on the mechanisms controlling migration along the dorsolateral path. In comparison, our understanding of the mechanisms controlling NCC migration along the ventral path are complicated by the fact that this population comprises multiple precursors that form different derivatives in distinct regions of the embryo. For example, ventrally migrating NCCs either stop within the sclerotome in close association with the neural tube to form neurons and glia of the sensory nervous system (i.e. the dorsal root ganglia [DRG]), while other NCCs continue to migrate further ventrally to form the autonomic nervous system (i.e. sympathetic ganglia and chromaffin cells of the adrenal gland)<br /> <br /> Adrenomedullary chromaffin cells are catecholamine (CA)-producing cells originating from trunk neural crest (NC) via sympathoadrenal progenitors (SAPs). We generated NC and SAPs from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) in vitro via BMP2/FGF2 exposure, ascertained by qPCR and immunoexpression of SOX10, ASCL1, TFAP2α, and PHOX2B, and by fluorescence-activated cell sorting selection for p75NTR and GD2, and confirmed their trunk-like HOX gene expression. We showed that continuing BMP4 and curtailing FGF2 in vitro, augmented with corticosteroid mimetic, induced these cells to upregulate the chromaffin cell-specific marker PNMT and other CA synthesis and storage markers, and we demonstrated noradrenaline and adrenaline by Faglu and high-performance liquid chromatography. We showed these human cells' SAP-like property of migration and differentiation into cells expressing chromaffin cell markers by implanting them into avian embryos in vivo and in chorio-allantoic membrane grafts. These cells have the potential for investigating differentiation of human chromaffin cells and for modeling diseases involving this cell type.<br /> <br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768882/<br /> <br /> ===Glossary===<br /> ----<br /> ===Reference list===</div>

Z5091101 https://embryology.med.unsw.edu.au/embryology/index.php?title=File:Differentiation_of_NCC.jpg&diff=356675 File:Differentiation of NCC.jpg 2018-10-10T07:31:58Z

<p>Z5091101: The neural crest cells become chromaffin precursor cells under exposure to BMP-4, and their growth and postnatal health is maintained by the secretion of glucocorticoids.</p> <hr /> <div>The neural crest cells become chromaffin precursor cells under exposure to BMP-4, and their growth and postnatal health is maintained by the secretion of glucocorticoids.</div>

Z5091101 https://embryology.med.unsw.edu.au/embryology/index.php?title=File:Trunk_NCC_migration.jpg&diff=356673 File:Trunk NCC migration.jpg 2018-10-10T07:28:45Z

<p>Z5091101: This image provides a basic picture of how the neural crest cells move to eventually reach the position where they differentiate into neural crest cells. This image was inspired by the following image: https://www.ncbi.nlm.nih.gov/books/NBK10065/figure...</p> <hr /> <div>This image provides a basic picture of how the neural crest cells move to eventually reach the position where they differentiate into neural crest cells. This image was inspired by the following image: https://www.ncbi.nlm.nih.gov/books/NBK10065/figure/A3118/?report=objectonly<br /> <br /> <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>.</div>

Z5091101 https://embryology.med.unsw.edu.au/embryology/index.php?title=2018_Group_Project_1&diff=356671 2018 Group Project 1 2018-10-10T06:51:25Z

<p>Z5091101: /* Embryonic origins */</p> <hr /> <div>=The Contribution of Neural Crest Cells to the Adrenal Medulla=<br /> ----<br /> {{2018ANAT2341ProjectHeader}}<br /> <br /> <br /> ===Introduction===<br /> [[User:Z5014972|Z5014972]] ([[User talk:Z5014972|talk]]) 12:47, 14 August 2018 (AEST)z5014972 <br /> good review article https://link.springer.com/article/10.1007%2Fs12022-009-9070-6<br /> ----<br /> <br /> <br /> The neural crest of an embryo differentiates and migrates to form various components of the body. One of these tissues is the medulla of the adrenal gland which is involved in the production of adrenalin and noradrenalin. This project will comprehensively outline the history of neural crest research, the embryonic developmental time course, tissue and organ structure, molecular mechanisms, abnormalities, animal models and current research.<br /> <br /> ===History===<br /> ----<br /> '''Describing the neural crest'''<br /> [[File:Wilhelm_His_History_Wilhelm.jpeg|left|230px|thumb|Wilhelm His]]<br /> The "neural crest" is a structure in the embryo and is the junction between the neural and epidermal ectoderm. It is exclusive to vertebrates and forms a range of structures{{#pmid:22230617|PMID22230617}}. The neural crest contributes a large number of cells of varying structure and function that directly or indirectly contribute to the development of tissues and organs within the body {{#pmid:19179766|PMID19179766}}. In 1868, the neural crest cells were first identified in a chick embryo as a collection of cells known as "Zwischenstrang" by Professor Wilhelm His {{#pmid:22820859|PMID22820859}}. Wilhelm His was among the first to provide an explanation for the mechanics governing the developing embryo as well as the physiology and the organs that the differing germinal regions would eventually give rise to. In 1878, the term neural ridge was used to describe this collection of cells but the term neural crest was later coined by Arthur Milnes Marshall in 1879 in a paper he worked on disseminating the knowledge from his research on the development of cranial nerves in chicken embryos. {{#pmid:19179766|PMID19179766}}.<br /> [[File:NC Location.jpg|left|450px|thumb|The neural crest]]<br /> <br /> '''1890s-1950s'''<br /> The neural crest is the point of origin for spinal/cranial ganglia and neurons. This theory received little criticism and was not contested much by other researchers prior to the 1890s. This is owing to the fact that the neural crest is quite closely related to the neural tube and thus this relationship makes sense. This discovery was made by His and Marshall, however, they found this out independently of one another.In the 1890s, Julia Platt, claimed that odontoblasts as well as the cartilages forming the facial and pharyngeal arch skeletons came from the ectoderm. This created much debate and was contested by many{{#pmid:22820859|PMID22820859}}. <br /> <br /> This is because this theory completely contradicted the germ-layer theory, whereby skeletal tissues originate at the mesoderm and not the ectoderm. The controversies this finding created brought about a slowing down of research, as demonstrated by a gap of almost 40 years between the theory that skeletal tissues originating from the neural crest. Today, it is known that the neural crest does indeed play a role in the development of the skeleton in vertebrates, particularly, the cranial neural crest. Although these studies were occurring, the focus was still primarily on researching pigment cells and ganglia of the spine up until the 1950s, when Sven Hörstadius' major work on the neural crest was published, titled "The Neural Crest: Its properties and derivatives in the light of experimental research". This work focused on experimental data tracing the development of the cartilaginous skeleton derived from the neural crest {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1960s - 1970s'''<br /> In the 1960s, the migration patterns of neural crest cells were studied in avian embryos (birds). This was a shift from studying the embryos of amphibians. This was inspired by studies conducted in the 1960s on neural crest cells migrating from the brain and spinal cord, known as trunk and cranial neural crest cells {{#pmid:19179766|PMID19179766}}. The cranial neural crest eventually becomes the bones, cartilage and connective tissues forming the foundation of the face, ears and teeth. The trunk neural crest cells can either become melanocytes or can migrate into sclerotomes which are later contributors to the cartilage of the spine and the dorsal root ganglia {{#pmid:22820859|PMID22820859}}. The cells in the trunk neural crest that migrate vertically become the sympathetic ganglia, the nerves proximal to the aorta and the adrenal medulla <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. In the 1970s many detailed maps signifying the pathways of many of the neural crest cells appeared as well as an understanding that the environment in which the neural crest cells are found plays a major role in their final development as well as the occurrences of abnormalities in the fetus {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1980s - 21st century'''<br /> [[File:Regions_of_NC_Cells.jpg|left|Neural crest regions|thumb]]<br /> From the 1980s-1990s, the causative agent of organ transformation from one to another (homeotic patterning), as well as the Hox genes which regulate the axis of most symmetrical animal embryos were founded and studied. The neural crest, which previously was divided into the cranial and trunk regions, was now further divided into the vagal and sacral neural crest, the cardiac neural crest and the cephalic neural crest {{#pmid:19179766|PMID19179766}}. The vagal & sacral neural crest gives rise to the parasympathetic ganglia found in the gut. Without these ganglia, peristalsis, is not possible <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. The cardiac neural crest contributes to the valves, septa and major blood vessels of the heart, as well as connective tissues and cartilage{{#pmid:19179766|PMID19179766}}. This is important for the structure of the heart as well as its overall function, enabling it to move blood around the body efficiently as well as keep pulmonary and aortic circulation separated <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> <br /> <br /> Today, knowledge of the neural crest cells, their migration patterns, modes of differentiation, derivatives and apoptosis (cell death) are being studied extensively. This is being done on a comparative basis between different organisms, to add further evidence for evolution {{#pmid:19179766|PMID19179766}}. The neural crest is definitely forging a "crest" between the fields of developmental and evolutionary biology, as it is a structure '''shared exclusively by all vertebrates'''. Invertebrates do not derive their specialised cells from the neural crest as they do not have one, rather, they derive these from the endomesoderm {{#pmid:22230617|PMID22230617}}.<br /> <br /> '''Future directions'''<br /> <br /> Since its discovery by His, the neural crest field has made great progress, from studies performed on the structure, to analysis of the molecules and whether certain aspects of the neural crest are specific to a single species of organism, or to all vertebrates collectively. Future work on the cranial neural crest needs to be done as well as identifying and categorising the networks responsible for the proliferation and death of cells, as well as how the cells move and migrate, as well as the gene regulatory networks (GRNs) that regulate the synthesis of proteins. Advances in technology will undeniable lead us to more answers on the subject {{#pmid:22230617|PMID22230617}}.<br /> <br /> ===Embryonic origins===<br /> ----<br /> https://www.ncbi.nlm.nih.gov/books/NBK10065/<br /> <br /> The adrenal gland is made up of the adrenal cortex and adrenal medulla, which both have different embryonic origins. The adrenal medulla arises from the neural crest tissue, found near the level of the coeliac plexus & sympathetic ganglion at somites 18-24 {{#pmid:16124976|PMID16124976}}. Specifically, this neural crest tissue comes from the trunk neural crest cells (see above figure to determine the approximate location in an embryo) <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> The trunk neural crest coordinates the development of the endocrine system, secretory cells, the peripheral nervous system and, to some degree, skeletal development, as well as innervation of the intestine {{#pmid: 28287247|PMID 28287247}}. The trunk neural cells arise caudally, undergo an epithelial to mesenchymal transition and follow three migratory pathways {{#pmid:20399766|PMID20399766}}.<br /> <br /> - A dorsolateral pathway (between ectoderm and somites), these become melanocytes, travel up to the point of the dermis and become a major part of the hair follicles and skin <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> - A ventrolateral pathway (through the somites)<br /> - A ventromedial pathway (between neural tube and posterior schlerotome){{#pmid:20399766|PMID20399766}}.<br /> <br /> Migration of neural crest cells from the sympathetic ganglion is what leads to the development of the adrenal medulla. In week 8 of development, immature cells called neuroblasts migrate through to the inner portion of the medulla, where they become the adrenal medulla {{#pmid:19683477|PMID19683477}}. Chromaffin cells are neuroendocrine cells and are found in the sympathetic ganglia and make up the majority of the adrenal medulla{{#pmid:19683477|PMID19683477}}. They synthesise and release a range of hormones in the body and arise from the temporary neural crest. The term chromaffin was inspired by the staining capacity of these cells when they came into contact with chrome salts. They make, store, export and use catecholamines, responsible for making noradrenaline and originate at the caudal region of somites 18-24 of the neural crest, also known as the adrenomedullary region {{#pmid:19683477|PMID19683477}}.<br /> <br /> For cells to leave the neural crest and begin their migration, certain conditions need to be met, that is, the cells need to be loosely connected, their tight junctions becoming relaxed, initiated by "Slug protein" and a loss of N-Cadherin which also leads to the loosening of these junctions. The surrounding matrix as well as chemotactic and stem cell factors of the neural tube are then what dictates how the neural crest cells move, some proteins stopping their migration to that area and others encouraging the movement <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. After splitting apart, the first neural crest cells move ventrally and pass into the spaces between the somites and then, through the anterior portions of each segment until they arrive at the para-aortic sites, where they become the cells of the sympathetic ganglia and the adrenal medulla {{#pmid:19683477|PMID19683477}}. BMP-4 (bone morphogenetic protein 4) then acts on these neural crest cells, preventing them from becoming cells that have a neural function and causing them to become chromaffin cells at the adrenal medulla. Glucocorticoids then play a role in maintenance of chromaffin cells in postnatal life, this was only found recently, as previously it was thought that glucocorticoids were responsible entirely for the differentiation of neural crest cells into chromaffin, or adrenomedullary cells {{#pmid:23220335|PMID23220335}}.<br /> <br /> ===Developmental time course===<br /> ----<br /> <br /> [[File:Adrenal_Medulla_Developmental_Timeline.jpg|right|thumb|500px]]<br /> <br /> The adrenal gland has two distinct sections, the cortex and the medulla, both with different embryonic origins. The cortex accounts for 90% of the adrenal glands and arises from intermediate mesoderm. The medulla only accounts for 10% of the adult adrenal glands, however it has neural crest embryonic origin. The medulla consists of chromaffinoblast cells which are migrant neuroblast cells from the neural crest, therefore the adrenal medulla is a component of the sympathetic nervous system.{{#pmid:21175739|PMID21175739}} Neural crest cells replicate in week 7 and begin to differentiate in week 8, the cells then migrate to the developing adrenal gland in week 9 of development.{{#pmid:25255746|PMID25255746}}{{#pmid:18279781|PMID18279781}} The neural crest cells infiltrate the cortex and the chromaffin cells are scattered islands in the cortex.{{#pmid:23354096|PMID23354096}} Throughout development the cells will become more compact in the centre of the gland, during this period of development the adrenal gland is growing rapidly. The gland is abnormally large until the second trimester and the medulla is much thicker prenatally.{{#pmid:18279781|PMID18279781}}{{#pmid:21175739|PMID21175739}}<br /> <br /> ===Developmental/adult function===<br /> ----<br /> ===Tissue and Organ structure===<br /> <br /> <br /> ====Normal Structure and Function of the Adrenal Medulla====<br /> <br /> The cells of the adrenal medulla are derived from the neural crest as opposed to the mesodermal origins of the cortex. The medulla contains secretory cells called chromaffin cells, due to the agents they produce when oxidised, such as chromate. These cells secrete epinephrine and norepinephrine in response to various substances such as acetylcholine.<br /> <br /> There are three types of cells in the adult adrenal medulla: <br /> 1) Epinephrine cells<br /> <br /> 2) Norepinephrine cells <br /> <br /> 3) Small granule-containing cells (SGCs)<br /> <br /> These cells also produce various other peptides such as substance P and neurotensin. The adrenal medulla also contains presynaptic sympathetic ganglion cells. {{#pmid:1694230|PMID1694230}}<br /> <br /> ====Related Anatomy====<br /> <br /> The tissue and organ structure of the adrenal medulla should be understood with regard to its specialised function within the sympathetic nervous system. <br /> <br /> The medullary region of the adrenal glands is tasked with the endocrine secretions of adrenaline and nor-adrenaline in response to environmental stressors that are signalled for by the sympathetic nervous system. That is, the secretion of fight-or-flight response hormones in order to restrict vasculature to the trunk and increase vascular activity in the peripheral musculature.<br /> <br /> The adrenal glands are supplied by several branches of the great vessels in the abdominal cavity. The secreted catecholamines in the medulla are directly able to pass to the blood stream this way.<br /> <br /> These adrenal glands and their contents are retroperitoneal in the adult and varied in shape, with the left often being semilunar and right being pyramidal. Nervous supply of the adrenal glands is achieved by contributions from the splanchnic nerves of the celiac plexus.<br /> <br /> <br /> ====Role of the Adrenal Medulla====<br /> <br /> Understanding the biochemistry of catecholamines is necessary to see how the adrenal medulla is designed in the stages of embryology and how it is suited for life in the neonate and adult. <br /> <br /> The epinephrine and norepinephrine in the neonate and adult work by primarily changing the osmoregulatory state of vasculature in organs. With the exclusion of their neuromodulatory and neurotransmitter functions, epinephrine and norepinephrine are mainly tasked with the control of sympathetic and parasympathetic supplies. <br /> <br /> Norepinephrine is a constrictor of peripheral vasculature by antagonising the action of surface receptors expressed on the endothelium of blood vessels, specifically Alpha-1 and Alpha-2 receptors, such that vascular resistance increases. <br /> <br /> Epinephrine is both a vasoconstrictor and vasodilator, depending on what receptors it attaches to. As a non-selective adrenergic agonist, it acts on Alpha-1, Alpha-2, Beta-1, Beta-2 and Beta-3 receptors that are found throughout the body's tissues, yielding many different physiological responses.<br /> <br /> <br /> [[File:Dd.jpg|500px|thumb|right|Adult Adrenal Glands in situ]] <br /> ----<br /> <br /> ===Molecular mechanisms/factors/genes===<br /> ----<br /> <br /> ====Genes and Transcription Factors Involved with the Adrenal Medulla's Development====<br /> <br /> Members of the SOX (SRY-Box) gene family have multiple key contributors to Neural Crest in the Adrenal Medulla.<br /> <br /> Mouse models have demonstrated that SOX-10 knock-outs (mice whose DNA has been engineered to not express SOX-10) do not have an adrenal medulla. There has also been suggestion that SOX-8,9 and 10 are all strongly related to the migratory patterning of neural crest cells to the developing adrenal glands.<br /> <br /> The TH gene (for Tyrosine Hydroxylase) encodes the aforementioned enzyme in the adrenal medulla and central nervous system. Tyrosine Hydroxylase is crucial in biochemical pathways and cascades for the synthesis of catecholamines and other CNS neurotransmitters. The conversion from L-Tyrosine to L-DOPA is dependent upon the catalytic action of Tyrosine Hydroxylase. From there, L-DOPA can make Dopamine and eventually Epinephrine and Norepinephrine as well. <br /> <br /> [[File:Catecholamine_Synthesis.jpg|500px|thumb|right|Cascade of Catecholamine Synthesis]]<br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2291442/<br /> https://www.ncbi.nlm.nih.gov/pubmed/19396395<br /> <br /> ===Abnormalities/abnormal development===<br /> ----<br /> ===Animal models===<br /> ----<br /> Animal models are an integral part of research in embryology. In particular due to the moral concerns regarding the use of humans in scientific research. As a result different animals are used as substitutes to simulate the same environments and hope to achieve results that would also be able to represent humans as well. Prenatal adrenal gland development has been described in a number of scientific reports dating from the 1900s to studies in more recent years. These involved a variety of animal models such as ox, sheep, swine and most commonly mice. <br /> <br /> ====Chromaffin cells =(in rat models)====<br /> There has been extensive research conducted into the adrenal chromaffin cells and their embryological developments. As explained above nueral crest cells are pluripotent meaning they are able to differentiate into multiple different cells. The neural crest cells give rise to chromaffin cells of the adrenal medulla.<br /> <br /> To study the formation process of the adrenal medulla in the embryonic period, we visualized chromaffin cells of rat embryos at 13 to 17 days of gestation using anti-tyrosine hydroxylase (TH) antiserum, and created three-dimensional images from serial tissue sections. Between 13 and 15 days of gestation, TH-positive cells (chromaffin cells) migrated from a group of TH-positive cells present dorsal to the adrenal primordium via the medial cranial end of the adrenal primordium into the adrenal primordium. At or after 16 days of gestation, the adrenal capsule was formed except on the ventral aspect of the cranial end of the adrenal gland, from which TH-positive cells penetrated into the adrenal gland.(Pubmed: 15240937) <br /> <br /> Ahonen suggested that some neural crest cells continue migration from the chain ganglia to the lateral sides of aorta, where they form the perirenal ganglia and adrenal medulla, and finally to the ventral side of the aorta to form the preaortic sympathetic tissue. However, that report only showed the several transverse sections of the fetal trunk for the a demonstration of the migration route of neural crest cells. In this study, using three dimensional reconstructed images, we aimed to observe how TH-labeled chromaffin cells penetrate into the adrenal anlage to form the adrenal medulla and whether the migration route of TH - positive cells from the adrenal connects the preaortic sympathetic ganglia <br /> (M.Yamato, R. Yanai, K. Arishima, 2004) <br /> <br /> Prenatal adrenal gland development has been described in numerous published reports covering a wide variety of species, including the ox (Katznelson, 1966; Wrobel and Suss, 1999), sheep (Davies, 1950; Wintour et al., 1975; Upadhyay and Zamboni, 1982; Naaman‐Reperant and Durand, 1997; Grino, 2004), swine (Sokolov et al., 2006) and mouse (Waring, 1935; Ikeda et al., 1994; Sass, 1996; Nyska and Maronpot, 1999; Bland et al., 2003; Val et al., 2007). Adrenal gland development also has been extensively described for humans as well (Kolliker, 1879; Minot, 1892; Zuckerkandl, 1912; Wieman, 1920; Ikeda et al., 1981; Langlois et al., 2002; Hanley and Arit, 2006).<br /> <br /> https://www.sciencedirect.com/science/article/pii/S0925477302004550<br /> http://dev.biologists.org/content/develop/126/13/2935.full.pdf<br /> <br /> ===Current research (labs)===<br /> ----<br /> The findings presented until now have focused on the mechanisms controlling migration along the dorsolateral path. In comparison, our understanding of the mechanisms controlling NCC migration along the ventral path are complicated by the fact that this population comprises multiple precursors that form different derivatives in distinct regions of the embryo. For example, ventrally migrating NCCs either stop within the sclerotome in close association with the neural tube to form neurons and glia of the sensory nervous system (i.e. the dorsal root ganglia [DRG]), while other NCCs continue to migrate further ventrally to form the autonomic nervous system (i.e. sympathetic ganglia and chromaffin cells of the adrenal gland)<br /> <br /> Adrenomedullary chromaffin cells are catecholamine (CA)-producing cells originating from trunk neural crest (NC) via sympathoadrenal progenitors (SAPs). We generated NC and SAPs from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) in vitro via BMP2/FGF2 exposure, ascertained by qPCR and immunoexpression of SOX10, ASCL1, TFAP2α, and PHOX2B, and by fluorescence-activated cell sorting selection for p75NTR and GD2, and confirmed their trunk-like HOX gene expression. We showed that continuing BMP4 and curtailing FGF2 in vitro, augmented with corticosteroid mimetic, induced these cells to upregulate the chromaffin cell-specific marker PNMT and other CA synthesis and storage markers, and we demonstrated noradrenaline and adrenaline by Faglu and high-performance liquid chromatography. We showed these human cells' SAP-like property of migration and differentiation into cells expressing chromaffin cell markers by implanting them into avian embryos in vivo and in chorio-allantoic membrane grafts. These cells have the potential for investigating differentiation of human chromaffin cells and for modeling diseases involving this cell type.<br /> <br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768882/<br /> <br /> ===Glossary===<br /> ----<br /> ===Reference list===</div>

Z5091101 https://embryology.med.unsw.edu.au/embryology/index.php?title=Talk:2018_Group_Project_1&diff=356669 Talk:2018 Group Project 1 2018-10-10T06:38:53Z

<p>Z5091101: /* embryonic origins */</p> <hr /> <div>==Adrenal Medulla Development==<br /> <br /> {{2018ANAT2341ProjectHeader}}<br /> {{2018ANAT2341ProjectDiscussion}}<br /> <br /> <br /> ==Peer Reviews (Lab 10)==<br /> [[User:Z5229431|Z5229431]] ([[User talk:Z5229431|talk]]) 16:14, 8 October 2018 (AEDT)<br /> The content under the history section is very well elaborated and thorough. It would be good to further develop the content in the rest of the sections similarly to what is being done in the history section. Under the subheading "Developmental time course", it will be nice to include a timeline for readers to better visualise the events occurring over the period of the development of the adrenal gland; a diagram works fine as well! <br /> <br /> There appears to be a lack of references under the section "Tissue/organ structure", but the content inside is well developed and progresses smoothly. Under "Molecular mechanisms/factors/genes", it would be great to clearly identify the type of transcription/growth factors that influences the differentiation of cell types in the adrenal medulla mentioned under "Tissue/organ structure". The transcription/growth factors can be divided into smaller subsections for each of the factor as well before further elaboration is made.<br /> <br /> Likewise, under the section "Animal models", subsections of the different animal models studied can be listed out, highlighting a few of the prominent key findings that are discovered on ox, sheep, swine and mice that was mentioned in the first paragraph of the section. It would be good to expand on all the findings and references listed in the last paragraph of the section and categorise them into the respective subsections.<br /> <br /> Overall, apart of the missing content in some of the subheadings, the overall flow of the information is smooth and easy to digest. With some tidying up of the reference links and further elaboration in the content, the page would be good to go! Keep pushing and include more images wherever possible because it really helps to grasp the interest of the readers and also make the content easier to comprehend. <br /> <br /> [[User:Z5229549|Z5229549]] ([[User talk:Z5229549|talk]]) 16:07, 6 October 2018 (AEST)<br /> Content on a whole was relatively smooth to read, not too much technical jargon that is often seen in more off-putting texts. The inclusion of self-drawn images brings a refreshing colour to the overall page, and seem rather accurate too, though the arrangement and positioning of the images and text could use some readjustment. <br /> <br /> However, there are still some headers that are lacking content, presumably still under editing and would be up soon. It also would be to some diagrams of the several experiments mentioned under animal models instead of just a large block of text. <br /> <br /> Overall, aside from several empty headers, the ones currently there more or less have the content nailed down, though several polishings and edits could be made. <br /> <br /> [[User:Z5229185|Z5229185]] ([[User talk:Z5229185|talk]]) 17:45, 4 October 2018 (AEST) I feel that the introduction sounded a bit off as referring to neural crest as a term seems rather inaccurate. A good history of the neural crest cells was provided and it is quite detailed (in fact it may be too detailed as it seems really long).<br /> <br /> I really like the hand drawing of the neural crest but I feel that it would look much better if you shifted the image to the right rather than let it take up the whole space.<br /> <br /> The content was pretty easy to follow and digest, so good job on that! You might want to take note on some errors in punctuation throughout the wiki page but since its just a draft, it isn't that big of an issue for now.<br /> <br /> The animal models section was really detailed and quite well written but the references need to be edited properly in the right format. I'm also a little confused as to why the picture of the "cascade of cathecholamine synthesis" is found right beside the Animal model section, you may want to adjust this!<br /> <br /> There are a few references present at the end of the page, but I assume this is because the other references have not been formatted properly yet. <br /> <br /> Overall good job with the page so far! I can see that the flow is some what smooth already (except for the empty sections) but just take note that there are still a few tweaks to be done with the referencing and placement of images! <br /> <br /> <br /> <br /> ** Perhaps describe the neural crest as a “structure” instead of a term. Great use of the student-drawn image as a guide! Overall, good simplified history. <br /> <br /> In the normal structure and function region; good but rather brief discussion of the physiology and structure. perhaps a little bit more, and maybe an image- unless you merge it with the related anatomy component. Really love the adult adrenal gland and the effort behind it. Only complaint would be that perhaps it would have been good to have the regions of the kidney (medulla, cortex etc). <br /> <br /> The description of the role of the adrenal medulla is very well-written; concise and seemingly accurate. Perhaps include the proper dot point structure instead of the >. The image drawn illustrating the cascade of catecholamine synthesis is also very good and I personally found it to be a helpful guide. However, it needs to be edited and correctly formatted for the webpage.<br /> <br /> The first two sentences of the animal models section may be combined into one. Proof-reading required eg. as explained above ‘nueral’! Who is Ahonen- Is an in-text reference needed here? Perhaps this paragraph belongs in the current research section as the animal used hasn’t been mentioned. Please review this bit as the information provided is good and relevant but maybe in the wrong section.<br /> <br /> In the current research section, the second sentence says ‘we generated’ … who are you referring to? The information here seems correct but was also quite advanced with numerous terms that I couldn’t understand- however it shows great research so well done!<br /> <br /> Overall, great work guys! Keep it up and move along with the project consistently! Perhaps include some images from the experiments you’ve described and some more high-tech images- although the ones you have drawn are also excellent! :) **<br /> <br /> <br /> [[User:Z5229281|Z5229281]] ([[User talk:Z5229281|talk]]) <br /> <br /> The beginning introduction is good and very detailed which is excellent as it shows adequate research has been applied but it may be too in depth as the project pertains to the adrenal medulla. But after reading it all it transitions nicely into the project so I don't mind all of the details that much. The information is organized and is well constructed in the first section of this project I like the time frames and each description under each, maybe use more than one reference for the intro so it is not all from one source. other than that the intro is really good.<br /> <br /> For the developmental adult section, it is either not researched or not started, I would just remove it as the rest of the project is put together and the adult function is not super important. Also, the developmental time course would be really cool to have to see the steps involved in the creation of the medulla, if not added not a big deal.<br /> <br /> The hand drawn figures are really nice add a certain flare to the project which i think is sweet.<br /> <br /> Other than that minor edits need to be made and this project is polished, some sections need to be researched more as there are still two weeks left until it is assessed, so plenty of time to polish.<br /> <br /> <br /> Group Project 1:<br /> The History section is very detailed - more weight on the history of neural crest discovery related to the adrenal medulla specifically would be appreciated, as this is your topic, but I do think that it is good that you have maintained a focus on neural crest.<br /> <br /> I think your section on genes and transcription factors is well described - I like that you have given a mouse model example. I presume the links to the sites will be added as proper references later. I also think the image of the cascade of catecholamine synthesis is helpful for those interested in the pathway, though its location is currently too far away from this section on the page. However, this is a minor issue and something that might be tidied up nearer the end of the assignment.<br /> <br /> You currently don’t have any abnormalities/abnormal development information. It would be nice to see some example here such as Congenital Adrenal Hyperplasia.<br /> <br /> In “current research” you have copied and pasted the introduction from the article cited. This definitely needs to be put into your own words, and maybe simplified as currently it is quite difficult to understand.<br /> <br /> <br /> This project is good because it appears to have a decent number of headings that they are going to address that covers all the aspects of the embryonic adrenal medulla. It has a very detailed history that the reader can easily follow, as well as a simple student drawn image which is good to see on the page. The developmental time course is brief and addresses what it needs to. There is also good information on the tissue structure and function, as well as on its role and the factors involved in its development. The project is also good in including animal model and current research examples. The two chalk diagrams are very detailed and easy to understand. <br /> <br /> The introduction has not been written yet, but that’s alright as it can be saved for the end of the project. Embryonic origin still needs to be written about, and should have a lot of information, as well as the abnormalities of development. The referencing is confusing at the bottom of each section and there should be more references in the reference list. There should also be images that aren’t student drawn and there should be more of them. The glossary also needs to be updated.<br /> <br /> In terms of improvements, maybe an educational video could be added about the origin of the adrenal medulla or the developmental time course. A list describing what the acronyms mean could also be really helpful to the reader. The arrangement of the images could be neater but that is saved for the end of the project.<br /> <br /> Overall. I think this is a really good project that shows a lot of effort and work being done as it is informative but easy to follow.<br /> <br /> <br /> [[User:Z5229597|Z5229597]] ([[User talk:Z5229597|talk]])<br /> Your project includes a lot of information and carefully chosen pictures and diagrams, but I think that more research needs to be conducted to extend the Reference list and to add more information to sections that are currently lacking. <br /> <br /> I am a little confused as to whether you are going to include a separate introduction paragraph, or if the history portion is where you want the reader to begin reading from. I think there needs to be some format editing to clarify this distinction. In regards to you history section, you include so much detailed information, but I believe that there is too much information that is irrelevant towards your specific topic. Even though its well organized and you share a lot of detail about the research history of neural crest, this section seems to be taking up a lot of space in your project. Even though you do mention adrenal medulla in your history section, it is not the focus and is only mentioned very briefly. Specific historical research that is directly about neural crest cell contribution directly to the adrenal medulla seems to be absent, but it should be the focal point.<br /> <br /> In regards to the Embryonic Origins section, there is currently only a link in one of the sections which needs to be replaced. Also, I think you include a lot of detail in the Developmental Time Course section, but it might be more clear to format that information as a timeline. As another formatting suggestion, if you are going to include a numbered list in your Tissue/Organ Structure, I don't think that it should be included directly in the paragraph. <br /> <br /> Your Molecular Mechanisms/Factors/Genes section and Animal Models section seem to both have relevant and appropriate information in them, but I believe that some subsections in them, such as Gene and Transcription Factors involved with Adrenal Medulla Development, need more information considering how integral these factor are to understanding how neural crest cells form the Adrenal Medulla. I think also the animal models section would benefit from a few subheadings, since it seems like there is a lot of information there but it is currently a little hard to follow. In both of these two sections though, I really enjoy the colorful image choices!<br /> <br /> There are still some links scattered throughout your page that aren't included in the reference section, and some of the sections still do not have any information under them.<br /> <br /> <br /> [[User:Z5229177|Z5229177]] ([[User talk:Z5229177|talk]]) 16:24, 8 October 2018 (AEDT)<br /> The history of neural crest was well-described and detailed, considering the different discoveries made. However, it is a too lengthy and would be good to link the history of adrenal medulla to neural crest under the history section as that should be the main focus of the project.<br /> <br /> For Developmental time course, I feel it might be good to have a timeline to show the different weeks of development and differentiation of the cortex and medulla to add on to the existing content that is already there. This might help readers to understand better.<br /> <br /> Sections such as embryonic origins, developmental/adult function, and abnormalities/abnormal development still needs to be worked on as they are currently empty and lacking content. <br /> <br /> Overall, the content is detailed and understandable by readers. Good job on the done parts and good use of the self-drawn figures! They are easy to understand and looks refreshing apart from the normal images or figures found online or on journal articles. Just need to brush up on those that have yet to be filled in, and also the references portion need to be listed out neatly.<br /> <br /> [[User:Z5229438|Z5229438]] ([[User talk:Z5229438|talk]])<br /> <br /> The history section seems to be off topic it goes into detail about the nueral crest alone when emphasis on the history behind the adrenal medulla would be more fit to the topic of your project.<br /> The embryonic origins section seems to have nothing underneath it .I am unsure if the developmental time course is a subheading to the embryonic origins section because the information provided under developmental time course seems to belong to the embryonic origins section. Sorting this out so that it is clear for the reader would be helpful.<br /> <br /> For the tissue structure and adult function portions there is nothing under the adult function but there is information about the adult function under the tissue structure as well , which is alspo confusing. The information is clear as to what it is talking about in the tissue structure section however its just confusing to know when the page will be talking about the adult function as it seems misplaced. The related anatomy under the tissue structure section is also well represented but seems to have no sources .<br /> <br /> The information under the mechanisms factors and genes section is very brief which is not an issue but some parts could use further explaining ,such as naming the multiple key contributors the SOX gene provides. There are also links provided and it may be helpful to explain what those links are so readers know what they are looking for when clicking on it.<br /> <br /> Abnormalities section is not written , and the animal models section looks good it presents good information that is easy to follow. I would just suggest adding references or links that describe what the link is before students click on it so it is clear .<br /> <br /> The current research lab section does not seem to talk about specifc research but more so a broad idea ,it will be helpful to have links to some of those research labs for students interested in following up , as well as a link that is labeled .<br /> <br /> Overall good start to the project it seems to need more research and more references throughout other than that its good.<br /> <br /> =Group 1 discussion:=<br /> <br /> ==introduction==<br /> [[User:Z5014972|Z5014972]] ([[User talk:Z5014972|talk]]) 12:47, 14 August 2018 (AEST)z5014972 <br /> <br /> A really good review article can be found here: https://link.springer.com/article/10.1007%2Fs12022-009-9070-6<br /> as well as here: https://www.jstage.jst.go.jp/article/jvms/66/6/66_6_635/_pdf ( [[User:Z5113627|Z5113627]] )<br /> ----<br /> ==history==<br /> ----<br /> https://www.ncbi.nlm.nih.gov/books/NBK10065/<br /> <br /> z5091101[[User:Z5091101|Z5091101]] ([[User talk:Z5091101|talk]]) 21:01, 25 August 2018 (AEST)<br /> <br /> [[User:Z5091101|Z5091101]] ([[User talk:Z5091101|talk]]) 17:29, 4 September 2018 (AEST)z5091101[[User:Z5091101|Z5091101]] ([[User talk:Z5091101|talk]]) 17:29, 4 September 2018 (AEST)<br /> <br /> <br /> <br /> A paper with some info on discovery/history https://www.ncbi.nlm.nih.gov/pubmed/19179766<br /> <br /> <br /> <br /> Can we please add normal anatomy of the adrenal medulla as a subheading - normal anatomy of adult medulla<br /> Was history referring to the history of discovery?<br /> <br /> [[User:Z5091101|Z5091101]] ([[User talk:Z5091101|talk]]) 11:46, 4 September 2018 (AEST)z5091101[[User:Z5091101|Z5091101]] ([[User talk:Z5091101|talk]]) 11:46, 4 September 2018 (AEST)<br /> <br /> <br /> <br /> https://www.researchgate.net/profile/Heather_Etchevers/publication/51681473_Primary_culture_of_chick_mouse_or_human_neural_crest_cells/links/0922b4f3d236fa8095000000/Primary-culture-of-chick-mouse-or-human-neural-crest-cells.pdf<br /> <br /> <br /> <br /> <br /> <br /> <br /> make a schematic drawing flow diagram outlining briefly history of neural crest<br /> <br /> <br /> <br /> <br /> History of endocrine development (add to intro)<br /> <br /> <br /> <br /> <br /> <br /> <br /> [[User:Z5091101|Z5091101]] ([[User talk:Z5091101|talk]]) 15:47, 12 September 2018 (AEST)z5091101[[User:Z5091101|Z5091101]] ([[User talk:Z5091101|talk]]) 15:47, 12 September 2018 (AEST)<br /> <br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3425661/<br /> <br /> <br /> https://onlinelibrary.wiley.com/doi/full/10.1002/dvdy.21513<br /> [[User:Z5091101|Z5091101]] ([[User talk:Z5091101|talk]]) 16:56, 12 September 2018 (AEST)z5091101[[User:Z5091101|Z5091101]] ([[User talk:Z5091101|talk]]) 16:56, 12 September 2018 (AEST)<br /> <br /> ==embryonic origins==<br /> ----<br /> [[User:Z5091101|Z5091101]] ([[User talk:Z5091101|talk]]) 11:46, 4 September 2018 (AEST)z5091101[[User:Z5091101|Z5091101]] ([[User talk:Z5091101|talk]]) 11:46, 4 September 2018 (AEST)<br /> https://clinicalgate.com/neural-crest/<br /> Want to upload either image<br /> - https://clinicalgate.com/neural-crest/<br /> - https://upload.wikimedia.org/wikipedia/commons/3/3d/Figure_43_06_01.jpg<br /> <br /> Origin is from neural crest cells; ectoderm<br /> <br /> <br /> <br /> <br /> <br /> https://link.springer.com/article/10.1007/s12038-008-0098-4<br /> <br /> Hey guys, do you think molecular mechanisms should be underneath embryonic origins and developmental time course before embryonic origins<br /> <br /> ==developmental time course== <br /> ----<br /> ----<br /> <br /> ==developmental/adult function== <br /> ----<br /> ==tissue/organ structure==<br /> <br /> The tissue and organ structure of the adrenal medulla should be understood with regard to its specialized function within the sympathetic nervous system. <br /> ----<br /> ==molecular mechanisms/factors/genes==<br /> <br /> {{#pmid:22031191|PMID22031191}}<br /> ----<br /> ==abnormalities/abnormal development==<br /> ----<br /> ==animal models==<br /> ----<br /> https://www.ncbi.nlm.nih.gov/pubmed/21175739<br /> <br /> Prenatal adrenal gland development has been described in numerous published reports covering a wide variety of species, including the ox (Katznelson, 1966; Wrobel and Suss, 1999), sheep (Davies, 1950; Wintour et al., 1975; Upadhyay and Zamboni, 1982; Naaman‐Reperant and Durand, 1997; Grino, 2004), swine (Sokolov et al., 2006) and mouse (Waring, 1935; Ikeda et al., 1994; Sass, 1996; Nyska and Maronpot, 1999; Bland et al., 2003; Val et al., 2007). Adrenal gland development also has been extensively described for humans as well (Kolliker, 1879; Minot, 1892; Zuckerkandl, 1912; Wieman, 1920; Ikeda et al., 1981; Langlois et al., 2002; Hanley and Arit, 2006), One‐Humped Camel (Camelus dromedarius)<br /> <br /> ==current research (labs)==<br /> ----<br /> ==glossary==<br /> ----<br /> ==reference list==<br /> ----<br /> [[User:Z5091101|Z5091101]] ([[User talk:Z5091101|talk]]) 11:40, 14 August 2018 (AEST)<br /> <br /> <br /> <br /> [[User:Z5113627|Z5113627]] <br /> <br /> {{#pmid:17350615|PMID17350615}}<br /> <br /> <br /> <br /> [[User:Z5014972|Z5014972]] ([[User talk:Z5014972|talk]]) 11:42, 14 August 2018 (AEST)z5014972<br /> <br /> Week 4 researching:<br /> *developmental time course<br /> *developmental/adult function<br /> *tissue/organ structure<br /> <br /> <br /> [[User:Z5112688|Z5112688]] ([[User talk:Z5112688|talk]]) 11:43, 14 August 2018 (AEST)Z5112688<br /> {{#pmid:22820859|PMID22820859}}<br /> {{#pmid:26038200|PMID26038200}}</div>

Z5091101 https://embryology.med.unsw.edu.au/embryology/index.php?title=2018_Group_Project_1&diff=356667 2018 Group Project 1 2018-10-10T06:36:21Z

<p>Z5091101: /* Embryonic origins */</p> <hr /> <div>=The Contribution of Neural Crest Cells to the Adrenal Medulla=<br /> ----<br /> {{2018ANAT2341ProjectHeader}}<br /> <br /> <br /> ===Introduction===<br /> [[User:Z5014972|Z5014972]] ([[User talk:Z5014972|talk]]) 12:47, 14 August 2018 (AEST)z5014972 <br /> good review article https://link.springer.com/article/10.1007%2Fs12022-009-9070-6<br /> ----<br /> <br /> <br /> The neural crest of an embryo differentiates and migrates to form various components of the body. One of these tissues is the medulla of the adrenal gland which is involved in the production of adrenalin and noradrenalin. This project will comprehensively outline the history of neural crest research, the embryonic developmental time course, tissue and organ structure, molecular mechanisms, abnormalities, animal models and current research.<br /> <br /> ===History===<br /> ----<br /> '''Describing the neural crest'''<br /> [[File:Wilhelm_His_History_Wilhelm.jpeg|left|230px|thumb|Wilhelm His]]<br /> The "neural crest" is a structure in the embryo and is the junction between the neural and epidermal ectoderm. It is exclusive to vertebrates and forms a range of structures{{#pmid:22230617|PMID22230617}}. The neural crest contributes a large number of cells of varying structure and function that directly or indirectly contribute to the development of tissues and organs within the body {{#pmid:19179766|PMID19179766}}. In 1868, the neural crest cells were first identified in a chick embryo as a collection of cells known as "Zwischenstrang" by Professor Wilhelm His {{#pmid:22820859|PMID22820859}}. Wilhelm His was among the first to provide an explanation for the mechanics governing the developing embryo as well as the physiology and the organs that the differing germinal regions would eventually give rise to. In 1878, the term neural ridge was used to describe this collection of cells but the term neural crest was later coined by Arthur Milnes Marshall in 1879 in a paper he worked on disseminating the knowledge from his research on the development of cranial nerves in chicken embryos. {{#pmid:19179766|PMID19179766}}.<br /> [[File:NC Location.jpg|left|450px|thumb|The neural crest]]<br /> <br /> '''1890s-1950s'''<br /> The neural crest is the point of origin for spinal/cranial ganglia and neurons. This theory received little criticism and was not contested much by other researchers prior to the 1890s. This is owing to the fact that the neural crest is quite closely related to the neural tube and thus this relationship makes sense. This discovery was made by His and Marshall, however, they found this out independently of one another.In the 1890s, Julia Platt, claimed that odontoblasts as well as the cartilages forming the facial and pharyngeal arch skeletons came from the ectoderm. This created much debate and was contested by many{{#pmid:22820859|PMID22820859}}. <br /> <br /> This is because this theory completely contradicted the germ-layer theory, whereby skeletal tissues originate at the mesoderm and not the ectoderm. The controversies this finding created brought about a slowing down of research, as demonstrated by a gap of almost 40 years between the theory that skeletal tissues originating from the neural crest. Today, it is known that the neural crest does indeed play a role in the development of the skeleton in vertebrates, particularly, the cranial neural crest. Although these studies were occurring, the focus was still primarily on researching pigment cells and ganglia of the spine up until the 1950s, when Sven Hörstadius' major work on the neural crest was published, titled "The Neural Crest: Its properties and derivatives in the light of experimental research". This work focused on experimental data tracing the development of the cartilaginous skeleton derived from the neural crest {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1960s - 1970s'''<br /> In the 1960s, the migration patterns of neural crest cells were studied in avian embryos (birds). This was a shift from studying the embryos of amphibians. This was inspired by studies conducted in the 1960s on neural crest cells migrating from the brain and spinal cord, known as trunk and cranial neural crest cells {{#pmid:19179766|PMID19179766}}. The cranial neural crest eventually becomes the bones, cartilage and connective tissues forming the foundation of the face, ears and teeth. The trunk neural crest cells can either become melanocytes or can migrate into sclerotomes which are later contributors to the cartilage of the spine and the dorsal root ganglia {{#pmid:22820859|PMID22820859}}. The cells in the trunk neural crest that migrate vertically become the sympathetic ganglia, the nerves proximal to the aorta and the adrenal medulla <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. In the 1970s many detailed maps signifying the pathways of many of the neural crest cells appeared as well as an understanding that the environment in which the neural crest cells are found plays a major role in their final development as well as the occurrences of abnormalities in the fetus {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1980s - 21st century'''<br /> [[File:Regions_of_NC_Cells.jpg|left|Neural crest regions|thumb]]<br /> From the 1980s-1990s, the causative agent of organ transformation from one to another (homeotic patterning), as well as the Hox genes which regulate the axis of most symmetrical animal embryos were founded and studied. The neural crest, which previously was divided into the cranial and trunk regions, was now further divided into the vagal and sacral neural crest, the cardiac neural crest and the cephalic neural crest {{#pmid:19179766|PMID19179766}}. The vagal & sacral neural crest gives rise to the parasympathetic ganglia found in the gut. Without these ganglia, peristalsis, is not possible <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. The cardiac neural crest contributes to the valves, septa and major blood vessels of the heart, as well as connective tissues and cartilage{{#pmid:19179766|PMID19179766}}. This is important for the structure of the heart as well as its overall function, enabling it to move blood around the body efficiently as well as keep pulmonary and aortic circulation separated <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> <br /> <br /> Today, knowledge of the neural crest cells, their migration patterns, modes of differentiation, derivatives and apoptosis (cell death) are being studied extensively. This is being done on a comparative basis between different organisms, to add further evidence for evolution {{#pmid:19179766|PMID19179766}}. The neural crest is definitely forging a "crest" between the fields of developmental and evolutionary biology, as it is a structure '''shared exclusively by all vertebrates'''. Invertebrates do not derive their specialised cells from the neural crest as they do not have one, rather, they derive these from the endomesoderm {{#pmid:22230617|PMID22230617}}.<br /> <br /> '''Future directions'''<br /> <br /> Since its discovery by His, the neural crest field has made great progress, from studies performed on the structure, to analysis of the molecules and whether certain aspects of the neural crest are specific to a single species of organism, or to all vertebrates collectively. Future work on the cranial neural crest needs to be done as well as identifying and categorising the networks responsible for the proliferation and death of cells, as well as how the cells move and migrate, as well as the gene regulatory networks (GRNs) that regulate the synthesis of proteins. Advances in technology will undeniable lead us to more answers on the subject {{#pmid:22230617|PMID22230617}}.<br /> <br /> ===Embryonic origins===<br /> ----<br /> https://www.ncbi.nlm.nih.gov/books/NBK10065/<br /> <br /> The adrenal gland is made up of the adrenal cortex and adrenal medulla, which both have different embryonic origins. The adrenal medulla arises from the neural crest tissue, found near the level of the coeliac plexus & sympathetic ganglion at somites 18-24 {{#pmid:16124976|PMID16124976}}. Specifically, this neural crest tissue comes from the trunk neural crest cells (see above figure to determine the approximate location in an embryo) <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> The trunk neural crest coordinates the development of the endocrine system, secretory cells, the peripheral nervous system and, to some degree, skeletal development, as well as innervation of the intestine {{#pmid: 28287247|PMID 28287247}}. The trunk neural cells arise caudally, undergo an epithelial to mesenchymal transition and follow three migratory pathways {{#pmid:20399766|PMID20399766}}.<br /> <br /> - A dorsolateral pathway (between ectoderm and somites), these become melanocytes, travel up to the point of the dermis and become a major part of the hair follicles and skin <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> - A ventrolateral pathway (through the somites)<br /> - A ventromedial pathway (between neural tube and posterior schlerotome){{#pmid:20399766|PMID20399766}}.<br /> <br /> Migration of neural crest cells from the sympathetic ganglion is what leads to the development of the adrenal medulla. In week 8 of development, immature cells called neuroblasts migrate through to the inner portion of the medulla, where they become the adrenal medulla {{#pmid:19683477|PMID19683477}}. Chromaffin cells are neuroendocrine cells and are found in the sympathetic ganglia and make up the majority of the adrenal medulla{{#pmid:19683477|PMID19683477}}. They synthesise and release a range of hormones in the body and arise from the temporary neural crest. The term chromaffin was inspired by the staining capacity of these cells when they came into contact with chrome salts. They make, store, export and use catecholamines, responsible for making noradrenaline and originate at the caudal region of somites 18-24 of the neural crest, also known as the adrenomedullary region {{#pmid:19683477|PMID19683477}}.<br /> <br /> For cells to leave the neural crest and begin their migration, certain conditions need to be met, that is, the cells need to be loosely connected, their tight junctions becoming relaxed, initiated by "Slug protein" and a loss of N-Cadherin which also leads to the loosening of these junctions. The surrounding matrix as well as chemotactic and stem cell factors of the neural tube are then what dictates how the neural crest cells move, some proteins stopping their migration to that area and others encouraging the movement <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. After splitting apart, the first neural crest cells move ventrally and pass into the spaces between the somites and then, through the anterior portions of each segment until they arrive at the para-aortic sites, where they become the cells of the sympathetic ganglia and the adrenal medulla {{#pmid:19683477|PMID19683477}}. BMP-4 (bone morphogenetic protein 4) then acts on these neural crest cells, preventing them from becoming cells that have a neural function and causing them to become chromaffin cells at the adrenal medulla. Glucocorticoids then play a role in further development of chromaffin cells in postnatal life, this was only found recently, as previously it was thought that glucocorticoids were responsible entirely for the differentiation of neural crest cells into chromaffin, or adrenomedullary cells {{#pmid:23220335|PMID23220335}}.<br /> <br /> ===Developmental time course===<br /> ----<br /> <br /> [[File:Adrenal_Medulla_Developmental_Timeline.jpg|right|thumb|500px]]<br /> <br /> The adrenal gland has two distinct sections, the cortex and the medulla, both with different embryonic origins. The cortex accounts for 90% of the adrenal glands and arises from intermediate mesoderm. The medulla only accounts for 10% of the adult adrenal glands, however it has neural crest embryonic origin. The medulla consists of chromaffinoblast cells which are migrant neuroblast cells from the neural crest, therefore the adrenal medulla is a component of the sympathetic nervous system.{{#pmid:21175739|PMID21175739}} Neural crest cells replicate in week 7 and begin to differentiate in week 8, the cells then migrate to the developing adrenal gland in week 9 of development.{{#pmid:25255746|PMID25255746}}{{#pmid:18279781|PMID18279781}} The neural crest cells infiltrate the cortex and the chromaffin cells are scattered islands in the cortex.{{#pmid:23354096|PMID23354096}} Throughout development the cells will become more compact in the centre of the gland, during this period of development the adrenal gland is growing rapidly. The gland is abnormally large until the second trimester and the medulla is much thicker prenatally.{{#pmid:18279781|PMID18279781}}{{#pmid:21175739|PMID21175739}}<br /> <br /> ===Developmental/adult function===<br /> ----<br /> ===Tissue and Organ structure===<br /> <br /> <br /> ====Normal Structure and Function of the Adrenal Medulla====<br /> <br /> The cells of the adrenal medulla are derived from the neural crest as opposed to the mesodermal origins of the cortex. The medulla contains secretory cells called chromaffin cells, due to the agents they produce when oxidised, such as chromate. These cells secrete epinephrine and norepinephrine in response to various substances such as acetylcholine.<br /> <br /> There are three types of cells in the adult adrenal medulla: <br /> 1) Epinephrine cells<br /> <br /> 2) Norepinephrine cells <br /> <br /> 3) Small granule-containing cells (SGCs)<br /> <br /> These cells also produce various other peptides such as substance P and neurotensin. The adrenal medulla also contains presynaptic sympathetic ganglion cells. {{#pmid:1694230|PMID1694230}}<br /> <br /> ====Related Anatomy====<br /> <br /> The tissue and organ structure of the adrenal medulla should be understood with regard to its specialised function within the sympathetic nervous system. <br /> <br /> The medullary region of the adrenal glands is tasked with the endocrine secretions of adrenaline and nor-adrenaline in response to environmental stressors that are signalled for by the sympathetic nervous system. That is, the secretion of fight-or-flight response hormones in order to restrict vasculature to the trunk and increase vascular activity in the peripheral musculature.<br /> <br /> The adrenal glands are supplied by several branches of the great vessels in the abdominal cavity. The secreted catecholamines in the medulla are directly able to pass to the blood stream this way.<br /> <br /> These adrenal glands and their contents are retroperitoneal in the adult and varied in shape, with the left often being semilunar and right being pyramidal. Nervous supply of the adrenal glands is achieved by contributions from the splanchnic nerves of the celiac plexus.<br /> <br /> <br /> ====Role of the Adrenal Medulla====<br /> <br /> Understanding the biochemistry of catecholamines is necessary to see how the adrenal medulla is designed in the stages of embryology and how it is suited for life in the neonate and adult. <br /> <br /> The epinephrine and norepinephrine in the neonate and adult work by primarily changing the osmoregulatory state of vasculature in organs. With the exclusion of their neuromodulatory and neurotransmitter functions, epinephrine and norepinephrine are mainly tasked with the control of sympathetic and parasympathetic supplies. <br /> <br /> Norepinephrine is a constrictor of peripheral vasculature by antagonising the action of surface receptors expressed on the endothelium of blood vessels, specifically Alpha-1 and Alpha-2 receptors, such that vascular resistance increases. <br /> <br /> Epinephrine is both a vasoconstrictor and vasodilator, depending on what receptors it attaches to. As a non-selective adrenergic agonist, it acts on Alpha-1, Alpha-2, Beta-1, Beta-2 and Beta-3 receptors that are found throughout the body's tissues, yielding many different physiological responses.<br /> <br /> <br /> [[File:Dd.jpg|500px|thumb|right|Adult Adrenal Glands in situ]] <br /> ----<br /> <br /> ===Molecular mechanisms/factors/genes===<br /> ----<br /> <br /> ====Genes and Transcription Factors Involved with the Adrenal Medulla's Development====<br /> <br /> Members of the SOX (SRY-Box) gene family have multiple key contributors to Neural Crest in the Adrenal Medulla.<br /> <br /> Mouse models have demonstrated that SOX-10 knock-outs (mice whose DNA has been engineered to not express SOX-10) do not have an adrenal medulla. There has also been suggestion that SOX-8,9 and 10 are all strongly related to the migratory patterning of neural crest cells to the developing adrenal glands.<br /> <br /> The TH gene (for Tyrosine Hydroxylase) encodes the aforementioned enzyme in the adrenal medulla and central nervous system. Tyrosine Hydroxylase is crucial in biochemical pathways and cascades for the synthesis of catecholamines and other CNS neurotransmitters. The conversion from L-Tyrosine to L-DOPA is dependent upon the catalytic action of Tyrosine Hydroxylase. From there, L-DOPA can make Dopamine and eventually Epinephrine and Norepinephrine as well. <br /> <br /> [[File:Catecholamine_Synthesis.jpg|500px|thumb|right|Cascade of Catecholamine Synthesis]]<br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2291442/<br /> https://www.ncbi.nlm.nih.gov/pubmed/19396395<br /> <br /> ===Abnormalities/abnormal development===<br /> ----<br /> ===Animal models===<br /> ----<br /> Animal models are an integral part of research in embryology. In particular due to the moral concerns regarding the use of humans in scientific research. As a result different animals are used as substitutes to simulate the same environments and hope to achieve results that would also be able to represent humans as well. Prenatal adrenal gland development has been described in a number of scientific reports dating from the 1900s to studies in more recent years. These involved a variety of animal models such as ox, sheep, swine and most commonly mice. <br /> <br /> ====Chromaffin cells =(in rat models)====<br /> There has been extensive research conducted into the adrenal chromaffin cells and their embryological developments. As explained above nueral crest cells are pluripotent meaning they are able to differentiate into multiple different cells. The neural crest cells give rise to chromaffin cells of the adrenal medulla.<br /> <br /> To study the formation process of the adrenal medulla in the embryonic period, we visualized chromaffin cells of rat embryos at 13 to 17 days of gestation using anti-tyrosine hydroxylase (TH) antiserum, and created three-dimensional images from serial tissue sections. Between 13 and 15 days of gestation, TH-positive cells (chromaffin cells) migrated from a group of TH-positive cells present dorsal to the adrenal primordium via the medial cranial end of the adrenal primordium into the adrenal primordium. At or after 16 days of gestation, the adrenal capsule was formed except on the ventral aspect of the cranial end of the adrenal gland, from which TH-positive cells penetrated into the adrenal gland.(Pubmed: 15240937) <br /> <br /> Ahonen suggested that some neural crest cells continue migration from the chain ganglia to the lateral sides of aorta, where they form the perirenal ganglia and adrenal medulla, and finally to the ventral side of the aorta to form the preaortic sympathetic tissue. However, that report only showed the several transverse sections of the fetal trunk for the a demonstration of the migration route of neural crest cells. In this study, using three dimensional reconstructed images, we aimed to observe how TH-labeled chromaffin cells penetrate into the adrenal anlage to form the adrenal medulla and whether the migration route of TH - positive cells from the adrenal connects the preaortic sympathetic ganglia <br /> (M.Yamato, R. Yanai, K. Arishima, 2004) <br /> <br /> Prenatal adrenal gland development has been described in numerous published reports covering a wide variety of species, including the ox (Katznelson, 1966; Wrobel and Suss, 1999), sheep (Davies, 1950; Wintour et al., 1975; Upadhyay and Zamboni, 1982; Naaman‐Reperant and Durand, 1997; Grino, 2004), swine (Sokolov et al., 2006) and mouse (Waring, 1935; Ikeda et al., 1994; Sass, 1996; Nyska and Maronpot, 1999; Bland et al., 2003; Val et al., 2007). Adrenal gland development also has been extensively described for humans as well (Kolliker, 1879; Minot, 1892; Zuckerkandl, 1912; Wieman, 1920; Ikeda et al., 1981; Langlois et al., 2002; Hanley and Arit, 2006).<br /> <br /> https://www.sciencedirect.com/science/article/pii/S0925477302004550<br /> http://dev.biologists.org/content/develop/126/13/2935.full.pdf<br /> <br /> ===Current research (labs)===<br /> ----<br /> The findings presented until now have focused on the mechanisms controlling migration along the dorsolateral path. In comparison, our understanding of the mechanisms controlling NCC migration along the ventral path are complicated by the fact that this population comprises multiple precursors that form different derivatives in distinct regions of the embryo. For example, ventrally migrating NCCs either stop within the sclerotome in close association with the neural tube to form neurons and glia of the sensory nervous system (i.e. the dorsal root ganglia [DRG]), while other NCCs continue to migrate further ventrally to form the autonomic nervous system (i.e. sympathetic ganglia and chromaffin cells of the adrenal gland)<br /> <br /> Adrenomedullary chromaffin cells are catecholamine (CA)-producing cells originating from trunk neural crest (NC) via sympathoadrenal progenitors (SAPs). We generated NC and SAPs from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) in vitro via BMP2/FGF2 exposure, ascertained by qPCR and immunoexpression of SOX10, ASCL1, TFAP2α, and PHOX2B, and by fluorescence-activated cell sorting selection for p75NTR and GD2, and confirmed their trunk-like HOX gene expression. We showed that continuing BMP4 and curtailing FGF2 in vitro, augmented with corticosteroid mimetic, induced these cells to upregulate the chromaffin cell-specific marker PNMT and other CA synthesis and storage markers, and we demonstrated noradrenaline and adrenaline by Faglu and high-performance liquid chromatography. We showed these human cells' SAP-like property of migration and differentiation into cells expressing chromaffin cell markers by implanting them into avian embryos in vivo and in chorio-allantoic membrane grafts. These cells have the potential for investigating differentiation of human chromaffin cells and for modeling diseases involving this cell type.<br /> <br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768882/<br /> <br /> ===Glossary===<br /> ----<br /> ===Reference list===</div>

Z5091101 https://embryology.med.unsw.edu.au/embryology/index.php?title=2018_Group_Project_1&diff=356665 2018 Group Project 1 2018-10-10T06:29:07Z

<p>Z5091101: /* Embryonic origins */</p> <hr /> <div>=The Contribution of Neural Crest Cells to the Adrenal Medulla=<br /> ----<br /> {{2018ANAT2341ProjectHeader}}<br /> <br /> <br /> ===Introduction===<br /> [[User:Z5014972|Z5014972]] ([[User talk:Z5014972|talk]]) 12:47, 14 August 2018 (AEST)z5014972 <br /> good review article https://link.springer.com/article/10.1007%2Fs12022-009-9070-6<br /> ----<br /> <br /> <br /> The neural crest of an embryo differentiates and migrates to form various components of the body. One of these tissues is the medulla of the adrenal gland which is involved in the production of adrenalin and noradrenalin. This project will comprehensively outline the history of neural crest research, the embryonic developmental time course, tissue and organ structure, molecular mechanisms, abnormalities, animal models and current research.<br /> <br /> ===History===<br /> ----<br /> '''Describing the neural crest'''<br /> [[File:Wilhelm_His_History_Wilhelm.jpeg|left|230px|thumb|Wilhelm His]]<br /> The "neural crest" is a structure in the embryo and is the junction between the neural and epidermal ectoderm. It is exclusive to vertebrates and forms a range of structures{{#pmid:22230617|PMID22230617}}. The neural crest contributes a large number of cells of varying structure and function that directly or indirectly contribute to the development of tissues and organs within the body {{#pmid:19179766|PMID19179766}}. In 1868, the neural crest cells were first identified in a chick embryo as a collection of cells known as "Zwischenstrang" by Professor Wilhelm His {{#pmid:22820859|PMID22820859}}. Wilhelm His was among the first to provide an explanation for the mechanics governing the developing embryo as well as the physiology and the organs that the differing germinal regions would eventually give rise to. In 1878, the term neural ridge was used to describe this collection of cells but the term neural crest was later coined by Arthur Milnes Marshall in 1879 in a paper he worked on disseminating the knowledge from his research on the development of cranial nerves in chicken embryos. {{#pmid:19179766|PMID19179766}}.<br /> [[File:NC Location.jpg|left|450px|thumb|The neural crest]]<br /> <br /> '''1890s-1950s'''<br /> The neural crest is the point of origin for spinal/cranial ganglia and neurons. This theory received little criticism and was not contested much by other researchers prior to the 1890s. This is owing to the fact that the neural crest is quite closely related to the neural tube and thus this relationship makes sense. This discovery was made by His and Marshall, however, they found this out independently of one another.In the 1890s, Julia Platt, claimed that odontoblasts as well as the cartilages forming the facial and pharyngeal arch skeletons came from the ectoderm. This created much debate and was contested by many{{#pmid:22820859|PMID22820859}}. <br /> <br /> This is because this theory completely contradicted the germ-layer theory, whereby skeletal tissues originate at the mesoderm and not the ectoderm. The controversies this finding created brought about a slowing down of research, as demonstrated by a gap of almost 40 years between the theory that skeletal tissues originating from the neural crest. Today, it is known that the neural crest does indeed play a role in the development of the skeleton in vertebrates, particularly, the cranial neural crest. Although these studies were occurring, the focus was still primarily on researching pigment cells and ganglia of the spine up until the 1950s, when Sven Hörstadius' major work on the neural crest was published, titled "The Neural Crest: Its properties and derivatives in the light of experimental research". This work focused on experimental data tracing the development of the cartilaginous skeleton derived from the neural crest {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1960s - 1970s'''<br /> In the 1960s, the migration patterns of neural crest cells were studied in avian embryos (birds). This was a shift from studying the embryos of amphibians. This was inspired by studies conducted in the 1960s on neural crest cells migrating from the brain and spinal cord, known as trunk and cranial neural crest cells {{#pmid:19179766|PMID19179766}}. The cranial neural crest eventually becomes the bones, cartilage and connective tissues forming the foundation of the face, ears and teeth. The trunk neural crest cells can either become melanocytes or can migrate into sclerotomes which are later contributors to the cartilage of the spine and the dorsal root ganglia {{#pmid:22820859|PMID22820859}}. The cells in the trunk neural crest that migrate vertically become the sympathetic ganglia, the nerves proximal to the aorta and the adrenal medulla <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. In the 1970s many detailed maps signifying the pathways of many of the neural crest cells appeared as well as an understanding that the environment in which the neural crest cells are found plays a major role in their final development as well as the occurrences of abnormalities in the fetus {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1980s - 21st century'''<br /> [[File:Regions_of_NC_Cells.jpg|left|Neural crest regions|thumb]]<br /> From the 1980s-1990s, the causative agent of organ transformation from one to another (homeotic patterning), as well as the Hox genes which regulate the axis of most symmetrical animal embryos were founded and studied. The neural crest, which previously was divided into the cranial and trunk regions, was now further divided into the vagal and sacral neural crest, the cardiac neural crest and the cephalic neural crest {{#pmid:19179766|PMID19179766}}. The vagal & sacral neural crest gives rise to the parasympathetic ganglia found in the gut. Without these ganglia, peristalsis, is not possible <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. The cardiac neural crest contributes to the valves, septa and major blood vessels of the heart, as well as connective tissues and cartilage{{#pmid:19179766|PMID19179766}}. This is important for the structure of the heart as well as its overall function, enabling it to move blood around the body efficiently as well as keep pulmonary and aortic circulation separated <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> <br /> <br /> Today, knowledge of the neural crest cells, their migration patterns, modes of differentiation, derivatives and apoptosis (cell death) are being studied extensively. This is being done on a comparative basis between different organisms, to add further evidence for evolution {{#pmid:19179766|PMID19179766}}. The neural crest is definitely forging a "crest" between the fields of developmental and evolutionary biology, as it is a structure '''shared exclusively by all vertebrates'''. Invertebrates do not derive their specialised cells from the neural crest as they do not have one, rather, they derive these from the endomesoderm {{#pmid:22230617|PMID22230617}}.<br /> <br /> '''Future directions'''<br /> <br /> Since its discovery by His, the neural crest field has made great progress, from studies performed on the structure, to analysis of the molecules and whether certain aspects of the neural crest are specific to a single species of organism, or to all vertebrates collectively. Future work on the cranial neural crest needs to be done as well as identifying and categorising the networks responsible for the proliferation and death of cells, as well as how the cells move and migrate, as well as the gene regulatory networks (GRNs) that regulate the synthesis of proteins. Advances in technology will undeniable lead us to more answers on the subject {{#pmid:22230617|PMID22230617}}.<br /> <br /> ===Embryonic origins===<br /> ----<br /> https://www.ncbi.nlm.nih.gov/books/NBK10065/<br /> <br /> The adrenal gland is made up of the adrenal cortex and adrenal medulla, which both have different embryonic origins. The adrenal medulla arises from the neural crest tissue, found near the level of the coeliac plexus & sympathetic ganglion at somites 18-24 {{#pmid:16124976|PMID16124976}}. Specifically, this neural crest tissue comes from the trunk neural crest cells (see above figure to determine the approximate location in an embryo) <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> The trunk neural crest coordinates the development of the endocrine system, secretory cells, the peripheral nervous system and, to some degree, skeletal development, as well as innervation of the intestine {{#pmid: 28287247|PMID 28287247}}. The trunk neural cells arise caudally, undergo an epithelial to mesenchymal transition and follow three migratory pathways {{#pmid:20399766|PMID20399766}}.<br /> <br /> - A dorsolateral pathway (between ectoderm and somites), these become melanocytes, travel up to the point of the dermis and become a major part of the hair follicles and skin <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> - A ventrolateral pathway (through the somites)<br /> - A ventromedial pathway (between neural tube and posterior schlerotome){{#pmid:20399766|PMID20399766}}.<br /> <br /> Migration of neural crest cells from the sympathetic ganglion is what leads to the development of the adrenal medulla. In week 8 of development, immature cells called neuroblasts migrate through to the inner portion of the medulla, where they become the adrenal medulla {{#pmid:19683477|PMID19683477}}. Chromaffin cells are neuroendocrine cells and are found in the sympathetic ganglia and make up the majority of the adrenal medulla{{#pmid:19683477|PMID19683477}}. They synthesise and release a range of hormones in the body and arise from the temporary neural crest. The term chromaffin was inspired by the staining capacity of these cells when they came into contact with chrome salts. They make, store, export and use catecholamines, responsible for making noradrenaline and originate at the caudal region of somites 18-24 of the neural crest, also known as the adrenomedullary region {{#pmid:19683477|PMID19683477}}.<br /> <br /> For cells to leave the neural crest and begin their migration, certain conditions need to be met, that is, the cells need to be loosely connected, their tight junctions becoming relaxed, initiated by "Slug protein" and a loss of N-Cadherin which also leads to the loosening of these junctions. The surrounding matrix as well as chemotactic and stem cell factors of the neural tube are then what dictates how the neural crest cells move, some proteins stopping their migration to that area and others encouraging the movement <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. After splitting apart, the first neural crest cells move ventrally and pass into the spaces between the somites and then, through the anterior portions of each segment until they arrive at the para-aortic sites, where they become the cells of the sympathetic ganglia and the adrenal medulla {{#pmid:19683477|PMID19683477}}. Glucocorticoids then act on these neural crest cells, preventing them from becoming cells that have a neural function and causing them to become chromaffin cells at the adrenal medulla <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>.<br /> <br /> ===Developmental time course===<br /> ----<br /> <br /> [[File:Adrenal_Medulla_Developmental_Timeline.jpg|right|thumb|500px]]<br /> <br /> The adrenal gland has two distinct sections, the cortex and the medulla, both with different embryonic origins. The cortex accounts for 90% of the adrenal glands and arises from intermediate mesoderm. The medulla only accounts for 10% of the adult adrenal glands, however it has neural crest embryonic origin. The medulla consists of chromaffinoblast cells which are migrant neuroblast cells from the neural crest, therefore the adrenal medulla is a component of the sympathetic nervous system.{{#pmid:21175739|PMID21175739}} Neural crest cells replicate in week 7 and begin to differentiate in week 8, the cells then migrate to the developing adrenal gland in week 9 of development.{{#pmid:25255746|PMID25255746}}{{#pmid:18279781|PMID18279781}} The neural crest cells infiltrate the cortex and the chromaffin cells are scattered islands in the cortex.{{#pmid:23354096|PMID23354096}} Throughout development the cells will become more compact in the centre of the gland, during this period of development the adrenal gland is growing rapidly. The gland is abnormally large until the second trimester and the medulla is much thicker prenatally.{{#pmid:18279781|PMID18279781}}{{#pmid:21175739|PMID21175739}}<br /> <br /> ===Developmental/adult function===<br /> ----<br /> ===Tissue and Organ structure===<br /> <br /> <br /> ====Normal Structure and Function of the Adrenal Medulla====<br /> <br /> The cells of the adrenal medulla are derived from the neural crest as opposed to the mesodermal origins of the cortex. The medulla contains secretory cells called chromaffin cells, due to the agents they produce when oxidised, such as chromate. These cells secrete epinephrine and norepinephrine in response to various substances such as acetylcholine.<br /> <br /> There are three types of cells in the adult adrenal medulla: <br /> 1) Epinephrine cells<br /> <br /> 2) Norepinephrine cells <br /> <br /> 3) Small granule-containing cells (SGCs)<br /> <br /> These cells also produce various other peptides such as substance P and neurotensin. The adrenal medulla also contains presynaptic sympathetic ganglion cells. {{#pmid:1694230|PMID1694230}}<br /> <br /> ====Related Anatomy====<br /> <br /> The tissue and organ structure of the adrenal medulla should be understood with regard to its specialised function within the sympathetic nervous system. <br /> <br /> The medullary region of the adrenal glands is tasked with the endocrine secretions of adrenaline and nor-adrenaline in response to environmental stressors that are signalled for by the sympathetic nervous system. That is, the secretion of fight-or-flight response hormones in order to restrict vasculature to the trunk and increase vascular activity in the peripheral musculature.<br /> <br /> The adrenal glands are supplied by several branches of the great vessels in the abdominal cavity. The secreted catecholamines in the medulla are directly able to pass to the blood stream this way.<br /> <br /> These adrenal glands and their contents are retroperitoneal in the adult and varied in shape, with the left often being semilunar and right being pyramidal. Nervous supply of the adrenal glands is achieved by contributions from the splanchnic nerves of the celiac plexus.<br /> <br /> <br /> ====Role of the Adrenal Medulla====<br /> <br /> Understanding the biochemistry of catecholamines is necessary to see how the adrenal medulla is designed in the stages of embryology and how it is suited for life in the neonate and adult. <br /> <br /> The epinephrine and norepinephrine in the neonate and adult work by primarily changing the osmoregulatory state of vasculature in organs. With the exclusion of their neuromodulatory and neurotransmitter functions, epinephrine and norepinephrine are mainly tasked with the control of sympathetic and parasympathetic supplies. <br /> <br /> Norepinephrine is a constrictor of peripheral vasculature by antagonising the action of surface receptors expressed on the endothelium of blood vessels, specifically Alpha-1 and Alpha-2 receptors, such that vascular resistance increases. <br /> <br /> Epinephrine is both a vasoconstrictor and vasodilator, depending on what receptors it attaches to. As a non-selective adrenergic agonist, it acts on Alpha-1, Alpha-2, Beta-1, Beta-2 and Beta-3 receptors that are found throughout the body's tissues, yielding many different physiological responses.<br /> <br /> <br /> [[File:Dd.jpg|500px|thumb|right|Adult Adrenal Glands in situ]] <br /> ----<br /> <br /> ===Molecular mechanisms/factors/genes===<br /> ----<br /> <br /> ====Genes and Transcription Factors Involved with the Adrenal Medulla's Development====<br /> <br /> Members of the SOX (SRY-Box) gene family have multiple key contributors to Neural Crest in the Adrenal Medulla.<br /> <br /> Mouse models have demonstrated that SOX-10 knock-outs (mice whose DNA has been engineered to not express SOX-10) do not have an adrenal medulla. There has also been suggestion that SOX-8,9 and 10 are all strongly related to the migratory patterning of neural crest cells to the developing adrenal glands.<br /> <br /> The TH gene (for Tyrosine Hydroxylase) encodes the aforementioned enzyme in the adrenal medulla and central nervous system. Tyrosine Hydroxylase is crucial in biochemical pathways and cascades for the synthesis of catecholamines and other CNS neurotransmitters. The conversion from L-Tyrosine to L-DOPA is dependent upon the catalytic action of Tyrosine Hydroxylase. From there, L-DOPA can make Dopamine and eventually Epinephrine and Norepinephrine as well. <br /> <br /> [[File:Catecholamine_Synthesis.jpg|500px|thumb|right|Cascade of Catecholamine Synthesis]]<br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2291442/<br /> https://www.ncbi.nlm.nih.gov/pubmed/19396395<br /> <br /> ===Abnormalities/abnormal development===<br /> ----<br /> ===Animal models===<br /> ----<br /> Animal models are an integral part of research in embryology. In particular due to the moral concerns regarding the use of humans in scientific research. As a result different animals are used as substitutes to simulate the same environments and hope to achieve results that would also be able to represent humans as well. Prenatal adrenal gland development has been described in a number of scientific reports dating from the 1900s to studies in more recent years. These involved a variety of animal models such as ox, sheep, swine and most commonly mice. <br /> <br /> ====Chromaffin cells =(in rat models)====<br /> There has been extensive research conducted into the adrenal chromaffin cells and their embryological developments. As explained above nueral crest cells are pluripotent meaning they are able to differentiate into multiple different cells. The neural crest cells give rise to chromaffin cells of the adrenal medulla.<br /> <br /> To study the formation process of the adrenal medulla in the embryonic period, we visualized chromaffin cells of rat embryos at 13 to 17 days of gestation using anti-tyrosine hydroxylase (TH) antiserum, and created three-dimensional images from serial tissue sections. Between 13 and 15 days of gestation, TH-positive cells (chromaffin cells) migrated from a group of TH-positive cells present dorsal to the adrenal primordium via the medial cranial end of the adrenal primordium into the adrenal primordium. At or after 16 days of gestation, the adrenal capsule was formed except on the ventral aspect of the cranial end of the adrenal gland, from which TH-positive cells penetrated into the adrenal gland.(Pubmed: 15240937) <br /> <br /> Ahonen suggested that some neural crest cells continue migration from the chain ganglia to the lateral sides of aorta, where they form the perirenal ganglia and adrenal medulla, and finally to the ventral side of the aorta to form the preaortic sympathetic tissue. However, that report only showed the several transverse sections of the fetal trunk for the a demonstration of the migration route of neural crest cells. In this study, using three dimensional reconstructed images, we aimed to observe how TH-labeled chromaffin cells penetrate into the adrenal anlage to form the adrenal medulla and whether the migration route of TH - positive cells from the adrenal connects the preaortic sympathetic ganglia <br /> (M.Yamato, R. Yanai, K. Arishima, 2004) <br /> <br /> Prenatal adrenal gland development has been described in numerous published reports covering a wide variety of species, including the ox (Katznelson, 1966; Wrobel and Suss, 1999), sheep (Davies, 1950; Wintour et al., 1975; Upadhyay and Zamboni, 1982; Naaman‐Reperant and Durand, 1997; Grino, 2004), swine (Sokolov et al., 2006) and mouse (Waring, 1935; Ikeda et al., 1994; Sass, 1996; Nyska and Maronpot, 1999; Bland et al., 2003; Val et al., 2007). Adrenal gland development also has been extensively described for humans as well (Kolliker, 1879; Minot, 1892; Zuckerkandl, 1912; Wieman, 1920; Ikeda et al., 1981; Langlois et al., 2002; Hanley and Arit, 2006).<br /> <br /> https://www.sciencedirect.com/science/article/pii/S0925477302004550<br /> http://dev.biologists.org/content/develop/126/13/2935.full.pdf<br /> <br /> ===Current research (labs)===<br /> ----<br /> The findings presented until now have focused on the mechanisms controlling migration along the dorsolateral path. In comparison, our understanding of the mechanisms controlling NCC migration along the ventral path are complicated by the fact that this population comprises multiple precursors that form different derivatives in distinct regions of the embryo. For example, ventrally migrating NCCs either stop within the sclerotome in close association with the neural tube to form neurons and glia of the sensory nervous system (i.e. the dorsal root ganglia [DRG]), while other NCCs continue to migrate further ventrally to form the autonomic nervous system (i.e. sympathetic ganglia and chromaffin cells of the adrenal gland)<br /> <br /> Adrenomedullary chromaffin cells are catecholamine (CA)-producing cells originating from trunk neural crest (NC) via sympathoadrenal progenitors (SAPs). We generated NC and SAPs from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) in vitro via BMP2/FGF2 exposure, ascertained by qPCR and immunoexpression of SOX10, ASCL1, TFAP2α, and PHOX2B, and by fluorescence-activated cell sorting selection for p75NTR and GD2, and confirmed their trunk-like HOX gene expression. We showed that continuing BMP4 and curtailing FGF2 in vitro, augmented with corticosteroid mimetic, induced these cells to upregulate the chromaffin cell-specific marker PNMT and other CA synthesis and storage markers, and we demonstrated noradrenaline and adrenaline by Faglu and high-performance liquid chromatography. We showed these human cells' SAP-like property of migration and differentiation into cells expressing chromaffin cell markers by implanting them into avian embryos in vivo and in chorio-allantoic membrane grafts. These cells have the potential for investigating differentiation of human chromaffin cells and for modeling diseases involving this cell type.<br /> <br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768882/<br /> <br /> ===Glossary===<br /> ----<br /> ===Reference list===</div>

Z5091101 https://embryology.med.unsw.edu.au/embryology/index.php?title=2018_Group_Project_1&diff=356663 2018 Group Project 1 2018-10-10T06:15:03Z

<p>Z5091101: /* Embryonic origins */</p> <hr /> <div>=The Contribution of Neural Crest Cells to the Adrenal Medulla=<br /> ----<br /> {{2018ANAT2341ProjectHeader}}<br /> <br /> <br /> ===Introduction===<br /> [[User:Z5014972|Z5014972]] ([[User talk:Z5014972|talk]]) 12:47, 14 August 2018 (AEST)z5014972 <br /> good review article https://link.springer.com/article/10.1007%2Fs12022-009-9070-6<br /> ----<br /> <br /> <br /> The neural crest of an embryo differentiates and migrates to form various components of the body. One of these tissues is the medulla of the adrenal gland which is involved in the production of adrenalin and noradrenalin. This project will comprehensively outline the history of neural crest research, the embryonic developmental time course, tissue and organ structure, molecular mechanisms, abnormalities, animal models and current research.<br /> <br /> ===History===<br /> ----<br /> '''Describing the neural crest'''<br /> [[File:Wilhelm_His_History_Wilhelm.jpeg|left|230px|thumb|Wilhelm His]]<br /> The "neural crest" is a structure in the embryo and is the junction between the neural and epidermal ectoderm. It is exclusive to vertebrates and forms a range of structures{{#pmid:22230617|PMID22230617}}. The neural crest contributes a large number of cells of varying structure and function that directly or indirectly contribute to the development of tissues and organs within the body {{#pmid:19179766|PMID19179766}}. In 1868, the neural crest cells were first identified in a chick embryo as a collection of cells known as "Zwischenstrang" by Professor Wilhelm His {{#pmid:22820859|PMID22820859}}. Wilhelm His was among the first to provide an explanation for the mechanics governing the developing embryo as well as the physiology and the organs that the differing germinal regions would eventually give rise to. In 1878, the term neural ridge was used to describe this collection of cells but the term neural crest was later coined by Arthur Milnes Marshall in 1879 in a paper he worked on disseminating the knowledge from his research on the development of cranial nerves in chicken embryos. {{#pmid:19179766|PMID19179766}}.<br /> [[File:NC Location.jpg|left|450px|thumb|The neural crest]]<br /> <br /> '''1890s-1950s'''<br /> The neural crest is the point of origin for spinal/cranial ganglia and neurons. This theory received little criticism and was not contested much by other researchers prior to the 1890s. This is owing to the fact that the neural crest is quite closely related to the neural tube and thus this relationship makes sense. This discovery was made by His and Marshall, however, they found this out independently of one another.In the 1890s, Julia Platt, claimed that odontoblasts as well as the cartilages forming the facial and pharyngeal arch skeletons came from the ectoderm. This created much debate and was contested by many{{#pmid:22820859|PMID22820859}}. <br /> <br /> This is because this theory completely contradicted the germ-layer theory, whereby skeletal tissues originate at the mesoderm and not the ectoderm. The controversies this finding created brought about a slowing down of research, as demonstrated by a gap of almost 40 years between the theory that skeletal tissues originating from the neural crest. Today, it is known that the neural crest does indeed play a role in the development of the skeleton in vertebrates, particularly, the cranial neural crest. Although these studies were occurring, the focus was still primarily on researching pigment cells and ganglia of the spine up until the 1950s, when Sven Hörstadius' major work on the neural crest was published, titled "The Neural Crest: Its properties and derivatives in the light of experimental research". This work focused on experimental data tracing the development of the cartilaginous skeleton derived from the neural crest {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1960s - 1970s'''<br /> In the 1960s, the migration patterns of neural crest cells were studied in avian embryos (birds). This was a shift from studying the embryos of amphibians. This was inspired by studies conducted in the 1960s on neural crest cells migrating from the brain and spinal cord, known as trunk and cranial neural crest cells {{#pmid:19179766|PMID19179766}}. The cranial neural crest eventually becomes the bones, cartilage and connective tissues forming the foundation of the face, ears and teeth. The trunk neural crest cells can either become melanocytes or can migrate into sclerotomes which are later contributors to the cartilage of the spine and the dorsal root ganglia {{#pmid:22820859|PMID22820859}}. The cells in the trunk neural crest that migrate vertically become the sympathetic ganglia, the nerves proximal to the aorta and the adrenal medulla <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. In the 1970s many detailed maps signifying the pathways of many of the neural crest cells appeared as well as an understanding that the environment in which the neural crest cells are found plays a major role in their final development as well as the occurrences of abnormalities in the fetus {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1980s - 21st century'''<br /> [[File:Regions_of_NC_Cells.jpg|left|Neural crest regions|thumb]]<br /> From the 1980s-1990s, the causative agent of organ transformation from one to another (homeotic patterning), as well as the Hox genes which regulate the axis of most symmetrical animal embryos were founded and studied. The neural crest, which previously was divided into the cranial and trunk regions, was now further divided into the vagal and sacral neural crest, the cardiac neural crest and the cephalic neural crest {{#pmid:19179766|PMID19179766}}. The vagal & sacral neural crest gives rise to the parasympathetic ganglia found in the gut. Without these ganglia, peristalsis, is not possible <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. The cardiac neural crest contributes to the valves, septa and major blood vessels of the heart, as well as connective tissues and cartilage{{#pmid:19179766|PMID19179766}}. This is important for the structure of the heart as well as its overall function, enabling it to move blood around the body efficiently as well as keep pulmonary and aortic circulation separated <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> <br /> <br /> Today, knowledge of the neural crest cells, their migration patterns, modes of differentiation, derivatives and apoptosis (cell death) are being studied extensively. This is being done on a comparative basis between different organisms, to add further evidence for evolution {{#pmid:19179766|PMID19179766}}. The neural crest is definitely forging a "crest" between the fields of developmental and evolutionary biology, as it is a structure '''shared exclusively by all vertebrates'''. Invertebrates do not derive their specialised cells from the neural crest as they do not have one, rather, they derive these from the endomesoderm {{#pmid:22230617|PMID22230617}}.<br /> <br /> '''Future directions'''<br /> <br /> Since its discovery by His, the neural crest field has made great progress, from studies performed on the structure, to analysis of the molecules and whether certain aspects of the neural crest are specific to a single species of organism, or to all vertebrates collectively. Future work on the cranial neural crest needs to be done as well as identifying and categorising the networks responsible for the proliferation and death of cells, as well as how the cells move and migrate, as well as the gene regulatory networks (GRNs) that regulate the synthesis of proteins. Advances in technology will undeniable lead us to more answers on the subject {{#pmid:22230617|PMID22230617}}.<br /> <br /> ===Embryonic origins===<br /> ----<br /> https://www.ncbi.nlm.nih.gov/books/NBK10065/<br /> <br /> The adrenal gland is made up of the adrenal cortex and adrenal medulla, which both have different embryonic origins. The adrenal medulla arises from the neural crest tissue, found near the level of the coeliac plexus & sympathetic ganglion at somites 18-24 {{#pmid:16124976|PMID16124976}}. Specifically, this neural crest tissue comes from the trunk neural crest cells (see above figure to determine the approximate location in an embryo) <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> The trunk neural crest coordinates the development of the endocrine system, secretory cells, the peripheral nervous system and, to some degree, skeletal development, as well as innervation of the intestine {{#pmid: 28287247|PMID 28287247}}. The trunk neural cells arise caudally, undergo an epithelial to mesenchymal transition and follow three migratory pathways {{#pmid:20399766|PMID20399766}}.<br /> <br /> - '''A dorsolateral pathway''' (between ectoderm and somites), these become melanocytes, travel up to the point of the dermis and become a major part of the hair follicles and skin <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> - A ventrolateral pathway (through the somites)<br /> - A ventromedial pathway (between neural tube and posterior schlerotome){{#pmid:20399766|PMID20399766}}.<br /> <br /> Migration of neural crest cells from the sympathetic ganglion is what leads to the development of the adrenal medulla. In week 8 of development, immature cells called neuroblasts migrate through to the inner portion of the medulla, where they become the adrenal medulla {{#pmid:19683477|PMID19683477}}. Chromaffin cells are neuroendocrine cells and are found in the sympathetic ganglia and make up the majority of the adrenal medulla{{#pmid:19683477|PMID19683477}}. They synthesise and release a range of hormones in the body and arise from the temporary neural crest. The term chromaffin was inspired by the staining capacity of these cells when they came into contact with chrome salts. They make, store, export and use catecholamines, responsible for making noradrenaline and originate at the caudal region of somites 18-24 of the neural crest, also known as the adrenomedullary region {{#pmid:19683477|PMID19683477}}.<br /> <br /> For cells to leave the neural crest and begin their migration, certain conditions need to be met, that is, the cells need to be loosely connected, their tight junctions becoming relaxed, initiated by "Slug protein" and a loss of N-Cadherin which also leads to the loosening of these junctions. The surrounding matrix as well as chemotactic and stem cell factors of the neural tube are then what dictates how the neural crest cells move, some proteins stopping their migration to that area and others encouraging the movement <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. After splitting apart, the first neural crest cells move ventrally and pass into the spaces between the somites and then, through the anterior portions of each segment until they arrive at the para-aortic sites, where they become the cells of the sympathetic ganglia and the adrenal medulla {{#pmid:19683477|PMID19683477}}.<br /> <br /> ===Developmental time course===<br /> ----<br /> <br /> [[File:Adrenal_Medulla_Developmental_Timeline.jpg|right|thumb|500px]]<br /> <br /> The adrenal gland has two distinct sections, the cortex and the medulla, both with different embryonic origins. The cortex accounts for 90% of the adrenal glands and arises from intermediate mesoderm. The medulla only accounts for 10% of the adult adrenal glands, however it has neural crest embryonic origin. The medulla consists of chromaffinoblast cells which are migrant neuroblast cells from the neural crest, therefore the adrenal medulla is a component of the sympathetic nervous system.{{#pmid:21175739|PMID21175739}} Neural crest cells replicate in week 7 and begin to differentiate in week 8, the cells then migrate to the developing adrenal gland in week 9 of development.{{#pmid:25255746|PMID25255746}}{{#pmid:18279781|PMID18279781}} The neural crest cells infiltrate the cortex and the chromaffin cells are scattered islands in the cortex.{{#pmid:23354096|PMID23354096}} Throughout development the cells will become more compact in the centre of the gland, during this period of development the adrenal gland is growing rapidly. The gland is abnormally large until the second trimester and the medulla is much thicker prenatally.{{#pmid:18279781|PMID18279781}}{{#pmid:21175739|PMID21175739}}<br /> <br /> ===Developmental/adult function===<br /> ----<br /> ===Tissue and Organ structure===<br /> <br /> <br /> ====Normal Structure and Function of the Adrenal Medulla====<br /> <br /> The cells of the adrenal medulla are derived from the neural crest as opposed to the mesodermal origins of the cortex. The medulla contains secretory cells called chromaffin cells, due to the agents they produce when oxidised, such as chromate. These cells secrete epinephrine and norepinephrine in response to various substances such as acetylcholine.<br /> <br /> There are three types of cells in the adult adrenal medulla: <br /> 1) Epinephrine cells<br /> <br /> 2) Norepinephrine cells <br /> <br /> 3) Small granule-containing cells (SGCs)<br /> <br /> These cells also produce various other peptides such as substance P and neurotensin. The adrenal medulla also contains presynaptic sympathetic ganglion cells. {{#pmid:1694230|PMID1694230}}<br /> <br /> ====Related Anatomy====<br /> <br /> The tissue and organ structure of the adrenal medulla should be understood with regard to its specialised function within the sympathetic nervous system. <br /> <br /> The medullary region of the adrenal glands is tasked with the endocrine secretions of adrenaline and nor-adrenaline in response to environmental stressors that are signalled for by the sympathetic nervous system. That is, the secretion of fight-or-flight response hormones in order to restrict vasculature to the trunk and increase vascular activity in the peripheral musculature.<br /> <br /> The adrenal glands are supplied by several branches of the great vessels in the abdominal cavity. The secreted catecholamines in the medulla are directly able to pass to the blood stream this way.<br /> <br /> These adrenal glands and their contents are retroperitoneal in the adult and varied in shape, with the left often being semilunar and right being pyramidal. Nervous supply of the adrenal glands is achieved by contributions from the splanchnic nerves of the celiac plexus.<br /> <br /> <br /> ====Role of the Adrenal Medulla====<br /> <br /> Understanding the biochemistry of catecholamines is necessary to see how the adrenal medulla is designed in the stages of embryology and how it is suited for life in the neonate and adult. <br /> <br /> The epinephrine and norepinephrine in the neonate and adult work by primarily changing the osmoregulatory state of vasculature in organs. With the exclusion of their neuromodulatory and neurotransmitter functions, epinephrine and norepinephrine are mainly tasked with the control of sympathetic and parasympathetic supplies. <br /> <br /> Norepinephrine is a constrictor of peripheral vasculature by antagonising the action of surface receptors expressed on the endothelium of blood vessels, specifically Alpha-1 and Alpha-2 receptors, such that vascular resistance increases. <br /> <br /> Epinephrine is both a vasoconstrictor and vasodilator, depending on what receptors it attaches to. As a non-selective adrenergic agonist, it acts on Alpha-1, Alpha-2, Beta-1, Beta-2 and Beta-3 receptors that are found throughout the body's tissues, yielding many different physiological responses.<br /> <br /> <br /> [[File:Dd.jpg|500px|thumb|right|Adult Adrenal Glands in situ]] <br /> ----<br /> <br /> ===Molecular mechanisms/factors/genes===<br /> ----<br /> <br /> ====Genes and Transcription Factors Involved with the Adrenal Medulla's Development====<br /> <br /> Members of the SOX (SRY-Box) gene family have multiple key contributors to Neural Crest in the Adrenal Medulla.<br /> <br /> Mouse models have demonstrated that SOX-10 knock-outs (mice whose DNA has been engineered to not express SOX-10) do not have an adrenal medulla. There has also been suggestion that SOX-8,9 and 10 are all strongly related to the migratory patterning of neural crest cells to the developing adrenal glands.<br /> <br /> The TH gene (for Tyrosine Hydroxylase) encodes the aforementioned enzyme in the adrenal medulla and central nervous system. Tyrosine Hydroxylase is crucial in biochemical pathways and cascades for the synthesis of catecholamines and other CNS neurotransmitters. The conversion from L-Tyrosine to L-DOPA is dependent upon the catalytic action of Tyrosine Hydroxylase. From there, L-DOPA can make Dopamine and eventually Epinephrine and Norepinephrine as well. <br /> <br /> [[File:Catecholamine_Synthesis.jpg|500px|thumb|right|Cascade of Catecholamine Synthesis]]<br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2291442/<br /> https://www.ncbi.nlm.nih.gov/pubmed/19396395<br /> <br /> ===Abnormalities/abnormal development===<br /> ----<br /> ===Animal models===<br /> ----<br /> Animal models are an integral part of research in embryology. In particular due to the moral concerns regarding the use of humans in scientific research. As a result different animals are used as substitutes to simulate the same environments and hope to achieve results that would also be able to represent humans as well. Prenatal adrenal gland development has been described in a number of scientific reports dating from the 1900s to studies in more recent years. These involved a variety of animal models such as ox, sheep, swine and most commonly mice. <br /> <br /> ====Chromaffin cells =(in rat models)====<br /> There has been extensive research conducted into the adrenal chromaffin cells and their embryological developments. As explained above nueral crest cells are pluripotent meaning they are able to differentiate into multiple different cells. The neural crest cells give rise to chromaffin cells of the adrenal medulla.<br /> <br /> To study the formation process of the adrenal medulla in the embryonic period, we visualized chromaffin cells of rat embryos at 13 to 17 days of gestation using anti-tyrosine hydroxylase (TH) antiserum, and created three-dimensional images from serial tissue sections. Between 13 and 15 days of gestation, TH-positive cells (chromaffin cells) migrated from a group of TH-positive cells present dorsal to the adrenal primordium via the medial cranial end of the adrenal primordium into the adrenal primordium. At or after 16 days of gestation, the adrenal capsule was formed except on the ventral aspect of the cranial end of the adrenal gland, from which TH-positive cells penetrated into the adrenal gland.(Pubmed: 15240937) <br /> <br /> Ahonen suggested that some neural crest cells continue migration from the chain ganglia to the lateral sides of aorta, where they form the perirenal ganglia and adrenal medulla, and finally to the ventral side of the aorta to form the preaortic sympathetic tissue. However, that report only showed the several transverse sections of the fetal trunk for the a demonstration of the migration route of neural crest cells. In this study, using three dimensional reconstructed images, we aimed to observe how TH-labeled chromaffin cells penetrate into the adrenal anlage to form the adrenal medulla and whether the migration route of TH - positive cells from the adrenal connects the preaortic sympathetic ganglia <br /> (M.Yamato, R. Yanai, K. Arishima, 2004) <br /> <br /> Prenatal adrenal gland development has been described in numerous published reports covering a wide variety of species, including the ox (Katznelson, 1966; Wrobel and Suss, 1999), sheep (Davies, 1950; Wintour et al., 1975; Upadhyay and Zamboni, 1982; Naaman‐Reperant and Durand, 1997; Grino, 2004), swine (Sokolov et al., 2006) and mouse (Waring, 1935; Ikeda et al., 1994; Sass, 1996; Nyska and Maronpot, 1999; Bland et al., 2003; Val et al., 2007). Adrenal gland development also has been extensively described for humans as well (Kolliker, 1879; Minot, 1892; Zuckerkandl, 1912; Wieman, 1920; Ikeda et al., 1981; Langlois et al., 2002; Hanley and Arit, 2006).<br /> <br /> https://www.sciencedirect.com/science/article/pii/S0925477302004550<br /> http://dev.biologists.org/content/develop/126/13/2935.full.pdf<br /> <br /> ===Current research (labs)===<br /> ----<br /> The findings presented until now have focused on the mechanisms controlling migration along the dorsolateral path. In comparison, our understanding of the mechanisms controlling NCC migration along the ventral path are complicated by the fact that this population comprises multiple precursors that form different derivatives in distinct regions of the embryo. For example, ventrally migrating NCCs either stop within the sclerotome in close association with the neural tube to form neurons and glia of the sensory nervous system (i.e. the dorsal root ganglia [DRG]), while other NCCs continue to migrate further ventrally to form the autonomic nervous system (i.e. sympathetic ganglia and chromaffin cells of the adrenal gland)<br /> <br /> Adrenomedullary chromaffin cells are catecholamine (CA)-producing cells originating from trunk neural crest (NC) via sympathoadrenal progenitors (SAPs). We generated NC and SAPs from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) in vitro via BMP2/FGF2 exposure, ascertained by qPCR and immunoexpression of SOX10, ASCL1, TFAP2α, and PHOX2B, and by fluorescence-activated cell sorting selection for p75NTR and GD2, and confirmed their trunk-like HOX gene expression. We showed that continuing BMP4 and curtailing FGF2 in vitro, augmented with corticosteroid mimetic, induced these cells to upregulate the chromaffin cell-specific marker PNMT and other CA synthesis and storage markers, and we demonstrated noradrenaline and adrenaline by Faglu and high-performance liquid chromatography. We showed these human cells' SAP-like property of migration and differentiation into cells expressing chromaffin cell markers by implanting them into avian embryos in vivo and in chorio-allantoic membrane grafts. These cells have the potential for investigating differentiation of human chromaffin cells and for modeling diseases involving this cell type.<br /> <br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768882/<br /> <br /> ===Glossary===<br /> ----<br /> ===Reference list===</div>

Z5091101 https://embryology.med.unsw.edu.au/embryology/index.php?title=2018_Group_Project_1&diff=356661 2018 Group Project 1 2018-10-10T06:04:02Z

<p>Z5091101: /* Embryonic origins */</p> <hr /> <div>=The Contribution of Neural Crest Cells to the Adrenal Medulla=<br /> ----<br /> {{2018ANAT2341ProjectHeader}}<br /> <br /> <br /> ===Introduction===<br /> [[User:Z5014972|Z5014972]] ([[User talk:Z5014972|talk]]) 12:47, 14 August 2018 (AEST)z5014972 <br /> good review article https://link.springer.com/article/10.1007%2Fs12022-009-9070-6<br /> ----<br /> <br /> <br /> The neural crest of an embryo differentiates and migrates to form various components of the body. One of these tissues is the medulla of the adrenal gland which is involved in the production of adrenalin and noradrenalin. This project will comprehensively outline the history of neural crest research, the embryonic developmental time course, tissue and organ structure, molecular mechanisms, abnormalities, animal models and current research.<br /> <br /> ===History===<br /> ----<br /> '''Describing the neural crest'''<br /> [[File:Wilhelm_His_History_Wilhelm.jpeg|left|230px|thumb|Wilhelm His]]<br /> The "neural crest" is a structure in the embryo and is the junction between the neural and epidermal ectoderm. It is exclusive to vertebrates and forms a range of structures{{#pmid:22230617|PMID22230617}}. The neural crest contributes a large number of cells of varying structure and function that directly or indirectly contribute to the development of tissues and organs within the body {{#pmid:19179766|PMID19179766}}. In 1868, the neural crest cells were first identified in a chick embryo as a collection of cells known as "Zwischenstrang" by Professor Wilhelm His {{#pmid:22820859|PMID22820859}}. Wilhelm His was among the first to provide an explanation for the mechanics governing the developing embryo as well as the physiology and the organs that the differing germinal regions would eventually give rise to. In 1878, the term neural ridge was used to describe this collection of cells but the term neural crest was later coined by Arthur Milnes Marshall in 1879 in a paper he worked on disseminating the knowledge from his research on the development of cranial nerves in chicken embryos. {{#pmid:19179766|PMID19179766}}.<br /> [[File:NC Location.jpg|left|450px|thumb|The neural crest]]<br /> <br /> '''1890s-1950s'''<br /> The neural crest is the point of origin for spinal/cranial ganglia and neurons. This theory received little criticism and was not contested much by other researchers prior to the 1890s. This is owing to the fact that the neural crest is quite closely related to the neural tube and thus this relationship makes sense. This discovery was made by His and Marshall, however, they found this out independently of one another.In the 1890s, Julia Platt, claimed that odontoblasts as well as the cartilages forming the facial and pharyngeal arch skeletons came from the ectoderm. This created much debate and was contested by many{{#pmid:22820859|PMID22820859}}. <br /> <br /> This is because this theory completely contradicted the germ-layer theory, whereby skeletal tissues originate at the mesoderm and not the ectoderm. The controversies this finding created brought about a slowing down of research, as demonstrated by a gap of almost 40 years between the theory that skeletal tissues originating from the neural crest. Today, it is known that the neural crest does indeed play a role in the development of the skeleton in vertebrates, particularly, the cranial neural crest. Although these studies were occurring, the focus was still primarily on researching pigment cells and ganglia of the spine up until the 1950s, when Sven Hörstadius' major work on the neural crest was published, titled "The Neural Crest: Its properties and derivatives in the light of experimental research". This work focused on experimental data tracing the development of the cartilaginous skeleton derived from the neural crest {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1960s - 1970s'''<br /> In the 1960s, the migration patterns of neural crest cells were studied in avian embryos (birds). This was a shift from studying the embryos of amphibians. This was inspired by studies conducted in the 1960s on neural crest cells migrating from the brain and spinal cord, known as trunk and cranial neural crest cells {{#pmid:19179766|PMID19179766}}. The cranial neural crest eventually becomes the bones, cartilage and connective tissues forming the foundation of the face, ears and teeth. The trunk neural crest cells can either become melanocytes or can migrate into sclerotomes which are later contributors to the cartilage of the spine and the dorsal root ganglia {{#pmid:22820859|PMID22820859}}. The cells in the trunk neural crest that migrate vertically become the sympathetic ganglia, the nerves proximal to the aorta and the adrenal medulla <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. In the 1970s many detailed maps signifying the pathways of many of the neural crest cells appeared as well as an understanding that the environment in which the neural crest cells are found plays a major role in their final development as well as the occurrences of abnormalities in the fetus {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1980s - 21st century'''<br /> [[File:Regions_of_NC_Cells.jpg|left|Neural crest regions|thumb]]<br /> From the 1980s-1990s, the causative agent of organ transformation from one to another (homeotic patterning), as well as the Hox genes which regulate the axis of most symmetrical animal embryos were founded and studied. The neural crest, which previously was divided into the cranial and trunk regions, was now further divided into the vagal and sacral neural crest, the cardiac neural crest and the cephalic neural crest {{#pmid:19179766|PMID19179766}}. The vagal & sacral neural crest gives rise to the parasympathetic ganglia found in the gut. Without these ganglia, peristalsis, is not possible <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. The cardiac neural crest contributes to the valves, septa and major blood vessels of the heart, as well as connective tissues and cartilage{{#pmid:19179766|PMID19179766}}. This is important for the structure of the heart as well as its overall function, enabling it to move blood around the body efficiently as well as keep pulmonary and aortic circulation separated <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> <br /> <br /> Today, knowledge of the neural crest cells, their migration patterns, modes of differentiation, derivatives and apoptosis (cell death) are being studied extensively. This is being done on a comparative basis between different organisms, to add further evidence for evolution {{#pmid:19179766|PMID19179766}}. The neural crest is definitely forging a "crest" between the fields of developmental and evolutionary biology, as it is a structure '''shared exclusively by all vertebrates'''. Invertebrates do not derive their specialised cells from the neural crest as they do not have one, rather, they derive these from the endomesoderm {{#pmid:22230617|PMID22230617}}.<br /> <br /> '''Future directions'''<br /> <br /> Since its discovery by His, the neural crest field has made great progress, from studies performed on the structure, to analysis of the molecules and whether certain aspects of the neural crest are specific to a single species of organism, or to all vertebrates collectively. Future work on the cranial neural crest needs to be done as well as identifying and categorising the networks responsible for the proliferation and death of cells, as well as how the cells move and migrate, as well as the gene regulatory networks (GRNs) that regulate the synthesis of proteins. Advances in technology will undeniable lead us to more answers on the subject {{#pmid:22230617|PMID22230617}}.<br /> <br /> ===Embryonic origins===<br /> ----<br /> https://www.ncbi.nlm.nih.gov/books/NBK10065/<br /> <br /> The adrenal gland is made up of the adrenal cortex and adrenal medulla, which both have different embryonic origins. The adrenal medulla arises from the neural crest tissue, found near the level of the coeliac plexus & sympathetic ganglion at somites 18-24 {{#pmid:16124976|PMID16124976}}. Specifically, this neural crest tissue comes from the trunk neural crest cells (see above figure to determine the approximate location in an embryo) <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> The trunk neural crest coordinates the development of the endocrine system, secretory cells, the peripheral nervous system and, to some degree, skeletal development, as well as innervation of the intestine {{#pmid: 28287247|PMID 28287247}}. The trunk neural cells arise caudally, undergo an epithelial to mesenchymal transition and follow three migratory pathways {{#pmid:20399766|PMID20399766}}.<br /> <br /> - '''A dorsolateral pathway''' (between ectoderm and somites), these become melanocytes, travel up to the point of the dermis and become a major part of the hair follicles and skin <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> - A ventrolateral pathway (through the somites)<br /> - A ventromedial pathway (between neural tube and posterior schlerotome){{#pmid:20399766|PMID20399766}}.<br /> <br /> Migration of neural crest cells from the sympathetic ganglion is what leads to the development of the adrenal medulla. In week 8 of development, immature cells called neuroblasts migrate through to the inner portion of the medulla, where they become the adrenal medulla {{#pmid:19683477|PMID19683477}}. Chromaffin cells are neuroendocrine cells and are found in the sympathetic ganglia and make up the majority of the adrenal medulla{{#pmid:19683477|PMID19683477}}. They synthesise and release a range of hormones in the body and arise from the temporary neural crest. The term chromaffin was inspired by the staining capacity of these cells when they came into contact with chrome salts. They make, store, export and use catecholamines, responsible for making noradrenaline and originate at the caudal region of somites 18-24 of the neural crest, also known as the adrenomedullary region {{#pmid:19683477|PMID19683477}}.<br /> <br /> For cells to leave the neural crest and begin their migration, certain conditions need to be met, that is, the cells need to be loosely connected, their tight junctions becoming relaxed, initiated by "Slug protein" and a loss of N-Cadherin which also leads to the loosening of these junctions. The surrounding matrix of the neural tube is then what dictates how the neural crest cells move, some proteins stopping their migration to that area and others encouraging the movement <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. After splitting apart, the first neural crest cells move ventrally and pass into the spaces between the somites and then, through the anterior portions of each segment until they arrive at the para-aortic sites {{#pmid:19683477|PMID19683477}}.<br /> <br /> ===Developmental time course===<br /> ----<br /> <br /> [[File:Adrenal_Medulla_Developmental_Timeline.jpg|right|thumb|500px]]<br /> <br /> The adrenal gland has two distinct sections, the cortex and the medulla, both with different embryonic origins. The cortex accounts for 90% of the adrenal glands and arises from intermediate mesoderm. The medulla only accounts for 10% of the adult adrenal glands, however it has neural crest embryonic origin. The medulla consists of chromaffinoblast cells which are migrant neuroblast cells from the neural crest, therefore the adrenal medulla is a component of the sympathetic nervous system.{{#pmid:21175739|PMID21175739}} Neural crest cells replicate in week 7 and begin to differentiate in week 8, the cells then migrate to the developing adrenal gland in week 9 of development.{{#pmid:25255746|PMID25255746}}{{#pmid:18279781|PMID18279781}} The neural crest cells infiltrate the cortex and the chromaffin cells are scattered islands in the cortex.{{#pmid:23354096|PMID23354096}} Throughout development the cells will become more compact in the centre of the gland, during this period of development the adrenal gland is growing rapidly. The gland is abnormally large until the second trimester and the medulla is much thicker prenatally.{{#pmid:18279781|PMID18279781}}{{#pmid:21175739|PMID21175739}}<br /> <br /> ===Developmental/adult function===<br /> ----<br /> ===Tissue and Organ structure===<br /> <br /> <br /> ====Normal Structure and Function of the Adrenal Medulla====<br /> <br /> The cells of the adrenal medulla are derived from the neural crest as opposed to the mesodermal origins of the cortex. The medulla contains secretory cells called chromaffin cells, due to the agents they produce when oxidised, such as chromate. These cells secrete epinephrine and norepinephrine in response to various substances such as acetylcholine.<br /> <br /> There are three types of cells in the adult adrenal medulla: <br /> 1) Epinephrine cells<br /> <br /> 2) Norepinephrine cells <br /> <br /> 3) Small granule-containing cells (SGCs)<br /> <br /> These cells also produce various other peptides such as substance P and neurotensin. The adrenal medulla also contains presynaptic sympathetic ganglion cells. {{#pmid:1694230|PMID1694230}}<br /> <br /> ====Related Anatomy====<br /> <br /> The tissue and organ structure of the adrenal medulla should be understood with regard to its specialised function within the sympathetic nervous system. <br /> <br /> The medullary region of the adrenal glands is tasked with the endocrine secretions of adrenaline and nor-adrenaline in response to environmental stressors that are signalled for by the sympathetic nervous system. That is, the secretion of fight-or-flight response hormones in order to restrict vasculature to the trunk and increase vascular activity in the peripheral musculature.<br /> <br /> The adrenal glands are supplied by several branches of the great vessels in the abdominal cavity. The secreted catecholamines in the medulla are directly able to pass to the blood stream this way.<br /> <br /> These adrenal glands and their contents are retroperitoneal in the adult and varied in shape, with the left often being semilunar and right being pyramidal. Nervous supply of the adrenal glands is achieved by contributions from the splanchnic nerves of the celiac plexus.<br /> <br /> <br /> ====Role of the Adrenal Medulla====<br /> <br /> Understanding the biochemistry of catecholamines is necessary to see how the adrenal medulla is designed in the stages of embryology and how it is suited for life in the neonate and adult. <br /> <br /> The epinephrine and norepinephrine in the neonate and adult work by primarily changing the osmoregulatory state of vasculature in organs. With the exclusion of their neuromodulatory and neurotransmitter functions, epinephrine and norepinephrine are mainly tasked with the control of sympathetic and parasympathetic supplies. <br /> <br /> Norepinephrine is a constrictor of peripheral vasculature by antagonising the action of surface receptors expressed on the endothelium of blood vessels, specifically Alpha-1 and Alpha-2 receptors, such that vascular resistance increases. <br /> <br /> Epinephrine is both a vasoconstrictor and vasodilator, depending on what receptors it attaches to. As a non-selective adrenergic agonist, it acts on Alpha-1, Alpha-2, Beta-1, Beta-2 and Beta-3 receptors that are found throughout the body's tissues, yielding many different physiological responses.<br /> <br /> <br /> [[File:Dd.jpg|500px|thumb|right|Adult Adrenal Glands in situ]] <br /> ----<br /> <br /> ===Molecular mechanisms/factors/genes===<br /> ----<br /> <br /> ====Genes and Transcription Factors Involved with the Adrenal Medulla's Development====<br /> <br /> Members of the SOX (SRY-Box) gene family have multiple key contributors to Neural Crest in the Adrenal Medulla.<br /> <br /> Mouse models have demonstrated that SOX-10 knock-outs (mice whose DNA has been engineered to not express SOX-10) do not have an adrenal medulla. There has also been suggestion that SOX-8,9 and 10 are all strongly related to the migratory patterning of neural crest cells to the developing adrenal glands.<br /> <br /> The TH gene (for Tyrosine Hydroxylase) encodes the aforementioned enzyme in the adrenal medulla and central nervous system. Tyrosine Hydroxylase is crucial in biochemical pathways and cascades for the synthesis of catecholamines and other CNS neurotransmitters. The conversion from L-Tyrosine to L-DOPA is dependent upon the catalytic action of Tyrosine Hydroxylase. From there, L-DOPA can make Dopamine and eventually Epinephrine and Norepinephrine as well. <br /> <br /> [[File:Catecholamine_Synthesis.jpg|500px|thumb|right|Cascade of Catecholamine Synthesis]]<br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2291442/<br /> https://www.ncbi.nlm.nih.gov/pubmed/19396395<br /> <br /> ===Abnormalities/abnormal development===<br /> ----<br /> ===Animal models===<br /> ----<br /> Animal models are an integral part of research in embryology. In particular due to the moral concerns regarding the use of humans in scientific research. As a result different animals are used as substitutes to simulate the same environments and hope to achieve results that would also be able to represent humans as well. Prenatal adrenal gland development has been described in a number of scientific reports dating from the 1900s to studies in more recent years. These involved a variety of animal models such as ox, sheep, swine and most commonly mice. <br /> <br /> ====Chromaffin cells =(in rat models)====<br /> There has been extensive research conducted into the adrenal chromaffin cells and their embryological developments. As explained above nueral crest cells are pluripotent meaning they are able to differentiate into multiple different cells. The neural crest cells give rise to chromaffin cells of the adrenal medulla.<br /> <br /> To study the formation process of the adrenal medulla in the embryonic period, we visualized chromaffin cells of rat embryos at 13 to 17 days of gestation using anti-tyrosine hydroxylase (TH) antiserum, and created three-dimensional images from serial tissue sections. Between 13 and 15 days of gestation, TH-positive cells (chromaffin cells) migrated from a group of TH-positive cells present dorsal to the adrenal primordium via the medial cranial end of the adrenal primordium into the adrenal primordium. At or after 16 days of gestation, the adrenal capsule was formed except on the ventral aspect of the cranial end of the adrenal gland, from which TH-positive cells penetrated into the adrenal gland.(Pubmed: 15240937) <br /> <br /> Ahonen suggested that some neural crest cells continue migration from the chain ganglia to the lateral sides of aorta, where they form the perirenal ganglia and adrenal medulla, and finally to the ventral side of the aorta to form the preaortic sympathetic tissue. However, that report only showed the several transverse sections of the fetal trunk for the a demonstration of the migration route of neural crest cells. In this study, using three dimensional reconstructed images, we aimed to observe how TH-labeled chromaffin cells penetrate into the adrenal anlage to form the adrenal medulla and whether the migration route of TH - positive cells from the adrenal connects the preaortic sympathetic ganglia <br /> (M.Yamato, R. Yanai, K. Arishima, 2004) <br /> <br /> Prenatal adrenal gland development has been described in numerous published reports covering a wide variety of species, including the ox (Katznelson, 1966; Wrobel and Suss, 1999), sheep (Davies, 1950; Wintour et al., 1975; Upadhyay and Zamboni, 1982; Naaman‐Reperant and Durand, 1997; Grino, 2004), swine (Sokolov et al., 2006) and mouse (Waring, 1935; Ikeda et al., 1994; Sass, 1996; Nyska and Maronpot, 1999; Bland et al., 2003; Val et al., 2007). Adrenal gland development also has been extensively described for humans as well (Kolliker, 1879; Minot, 1892; Zuckerkandl, 1912; Wieman, 1920; Ikeda et al., 1981; Langlois et al., 2002; Hanley and Arit, 2006).<br /> <br /> https://www.sciencedirect.com/science/article/pii/S0925477302004550<br /> http://dev.biologists.org/content/develop/126/13/2935.full.pdf<br /> <br /> ===Current research (labs)===<br /> ----<br /> The findings presented until now have focused on the mechanisms controlling migration along the dorsolateral path. In comparison, our understanding of the mechanisms controlling NCC migration along the ventral path are complicated by the fact that this population comprises multiple precursors that form different derivatives in distinct regions of the embryo. For example, ventrally migrating NCCs either stop within the sclerotome in close association with the neural tube to form neurons and glia of the sensory nervous system (i.e. the dorsal root ganglia [DRG]), while other NCCs continue to migrate further ventrally to form the autonomic nervous system (i.e. sympathetic ganglia and chromaffin cells of the adrenal gland)<br /> <br /> Adrenomedullary chromaffin cells are catecholamine (CA)-producing cells originating from trunk neural crest (NC) via sympathoadrenal progenitors (SAPs). We generated NC and SAPs from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) in vitro via BMP2/FGF2 exposure, ascertained by qPCR and immunoexpression of SOX10, ASCL1, TFAP2α, and PHOX2B, and by fluorescence-activated cell sorting selection for p75NTR and GD2, and confirmed their trunk-like HOX gene expression. We showed that continuing BMP4 and curtailing FGF2 in vitro, augmented with corticosteroid mimetic, induced these cells to upregulate the chromaffin cell-specific marker PNMT and other CA synthesis and storage markers, and we demonstrated noradrenaline and adrenaline by Faglu and high-performance liquid chromatography. We showed these human cells' SAP-like property of migration and differentiation into cells expressing chromaffin cell markers by implanting them into avian embryos in vivo and in chorio-allantoic membrane grafts. These cells have the potential for investigating differentiation of human chromaffin cells and for modeling diseases involving this cell type.<br /> <br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768882/<br /> <br /> ===Glossary===<br /> ----<br /> ===Reference list===</div>

Z5091101 https://embryology.med.unsw.edu.au/embryology/index.php?title=2018_Group_Project_1&diff=356659 2018 Group Project 1 2018-10-10T03:28:44Z

<p>Z5091101: /* Embryonic origins */</p> <hr /> <div>=The Contribution of Neural Crest Cells to the Adrenal Medulla=<br /> ----<br /> {{2018ANAT2341ProjectHeader}}<br /> <br /> <br /> ===Introduction===<br /> [[User:Z5014972|Z5014972]] ([[User talk:Z5014972|talk]]) 12:47, 14 August 2018 (AEST)z5014972 <br /> good review article https://link.springer.com/article/10.1007%2Fs12022-009-9070-6<br /> ----<br /> <br /> <br /> The neural crest of an embryo differentiates and migrates to form various components of the body. One of these tissues is the medulla of the adrenal gland which is involved in the production of adrenalin and noradrenalin. This project will comprehensively outline the history of neural crest research, the embryonic developmental time course, tissue and organ structure, molecular mechanisms, abnormalities, animal models and current research.<br /> <br /> ===History===<br /> ----<br /> '''Describing the neural crest'''<br /> [[File:Wilhelm_His_History_Wilhelm.jpeg|left|230px|thumb|Wilhelm His]]<br /> The "neural crest" is a structure in the embryo and is the junction between the neural and epidermal ectoderm. It is exclusive to vertebrates and forms a range of structures{{#pmid:22230617|PMID22230617}}. The neural crest contributes a large number of cells of varying structure and function that directly or indirectly contribute to the development of tissues and organs within the body {{#pmid:19179766|PMID19179766}}. In 1868, the neural crest cells were first identified in a chick embryo as a collection of cells known as "Zwischenstrang" by Professor Wilhelm His {{#pmid:22820859|PMID22820859}}. Wilhelm His was among the first to provide an explanation for the mechanics governing the developing embryo as well as the physiology and the organs that the differing germinal regions would eventually give rise to. In 1878, the term neural ridge was used to describe this collection of cells but the term neural crest was later coined by Arthur Milnes Marshall in 1879 in a paper he worked on disseminating the knowledge from his research on the development of cranial nerves in chicken embryos. {{#pmid:19179766|PMID19179766}}.<br /> [[File:NC Location.jpg|left|450px|thumb|The neural crest]]<br /> <br /> '''1890s-1950s'''<br /> The neural crest is the point of origin for spinal/cranial ganglia and neurons. This theory received little criticism and was not contested much by other researchers prior to the 1890s. This is owing to the fact that the neural crest is quite closely related to the neural tube and thus this relationship makes sense. This discovery was made by His and Marshall, however, they found this out independently of one another.In the 1890s, Julia Platt, claimed that odontoblasts as well as the cartilages forming the facial and pharyngeal arch skeletons came from the ectoderm. This created much debate and was contested by many{{#pmid:22820859|PMID22820859}}. <br /> <br /> This is because this theory completely contradicted the germ-layer theory, whereby skeletal tissues originate at the mesoderm and not the ectoderm. The controversies this finding created brought about a slowing down of research, as demonstrated by a gap of almost 40 years between the theory that skeletal tissues originating from the neural crest. Today, it is known that the neural crest does indeed play a role in the development of the skeleton in vertebrates, particularly, the cranial neural crest. Although these studies were occurring, the focus was still primarily on researching pigment cells and ganglia of the spine up until the 1950s, when Sven Hörstadius' major work on the neural crest was published, titled "The Neural Crest: Its properties and derivatives in the light of experimental research". This work focused on experimental data tracing the development of the cartilaginous skeleton derived from the neural crest {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1960s - 1970s'''<br /> In the 1960s, the migration patterns of neural crest cells were studied in avian embryos (birds). This was a shift from studying the embryos of amphibians. This was inspired by studies conducted in the 1960s on neural crest cells migrating from the brain and spinal cord, known as trunk and cranial neural crest cells {{#pmid:19179766|PMID19179766}}. The cranial neural crest eventually becomes the bones, cartilage and connective tissues forming the foundation of the face, ears and teeth. The trunk neural crest cells can either become melanocytes or can migrate into sclerotomes which are later contributors to the cartilage of the spine and the dorsal root ganglia {{#pmid:22820859|PMID22820859}}. The cells in the trunk neural crest that migrate vertically become the sympathetic ganglia, the nerves proximal to the aorta and the adrenal medulla <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. In the 1970s many detailed maps signifying the pathways of many of the neural crest cells appeared as well as an understanding that the environment in which the neural crest cells are found plays a major role in their final development as well as the occurrences of abnormalities in the fetus {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1980s - 21st century'''<br /> [[File:Regions_of_NC_Cells.jpg|left|Neural crest regions|thumb]]<br /> From the 1980s-1990s, the causative agent of organ transformation from one to another (homeotic patterning), as well as the Hox genes which regulate the axis of most symmetrical animal embryos were founded and studied. The neural crest, which previously was divided into the cranial and trunk regions, was now further divided into the vagal and sacral neural crest, the cardiac neural crest and the cephalic neural crest {{#pmid:19179766|PMID19179766}}. The vagal & sacral neural crest gives rise to the parasympathetic ganglia found in the gut. Without these ganglia, peristalsis, is not possible <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. The cardiac neural crest contributes to the valves, septa and major blood vessels of the heart, as well as connective tissues and cartilage{{#pmid:19179766|PMID19179766}}. This is important for the structure of the heart as well as its overall function, enabling it to move blood around the body efficiently as well as keep pulmonary and aortic circulation separated <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> <br /> <br /> Today, knowledge of the neural crest cells, their migration patterns, modes of differentiation, derivatives and apoptosis (cell death) are being studied extensively. This is being done on a comparative basis between different organisms, to add further evidence for evolution {{#pmid:19179766|PMID19179766}}. The neural crest is definitely forging a "crest" between the fields of developmental and evolutionary biology, as it is a structure '''shared exclusively by all vertebrates'''. Invertebrates do not derive their specialised cells from the neural crest as they do not have one, rather, they derive these from the endomesoderm {{#pmid:22230617|PMID22230617}}.<br /> <br /> '''Future directions'''<br /> <br /> Since its discovery by His, the neural crest field has made great progress, from studies performed on the structure, to analysis of the molecules and whether certain aspects of the neural crest are specific to a single species of organism, or to all vertebrates collectively. Future work on the cranial neural crest needs to be done as well as identifying and categorising the networks responsible for the proliferation and death of cells, as well as how the cells move and migrate, as well as the gene regulatory networks (GRNs) that regulate the synthesis of proteins. Advances in technology will undeniable lead us to more answers on the subject {{#pmid:22230617|PMID22230617}}.<br /> <br /> ===Embryonic origins===<br /> ----<br /> https://www.ncbi.nlm.nih.gov/books/NBK10065/<br /> <br /> The adrenal gland is made up of the adrenal cortex and adrenal medulla, which both have different embryonic origins. The adrenal medulla arises from the neural crest tissue, found near the level of the coeliac plexus & sympathetic ganglion at somites 18-24 {{#pmid:16124976|PMID16124976}}. Specifically, this neural crest tissue comes from the trunk neural crest cells (see above figure to determine the approximate location in an embryo) <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> The trunk neural crest coordinates the development of the endocrine system, secretory cells, the peripheral nervous system and, to some degree, skeletal development, as well as innervation of the intestine {{#pmid: 28287247|PMID 28287247}}. The trunk neural cells arise caudally, undergo an epithelial to mesenchymal transition and follow three migratory pathways {{#pmid:20399766|PMID20399766}}.<br /> <br /> - '''A dorsolateral pathway''' (between ectoderm and somites), these become melanocytes, travel up to the point of the dermis and become a major part of the hair follicles and skin <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> - A ventrolateral pathway (through the somites)<br /> - A ventromedial pathway (between neural tube and posterior schlerotome){{#pmid:20399766|PMID20399766}}.<br /> <br /> Migration of neural crest cells from the sympathetic ganglion is what leads to the development of the adrenal medulla. In week 8 of development, immature cells called neuroblasts migrate through to the inner portion of the medulla, where they become the adrenal medulla {{#pmid:19683477|PMID19683477}}. Chromaffin cells are neuroendocrine cells and are found in the sympathetic ganglia and make up the majority of the adrenal medulla{{#pmid:19683477|PMID19683477}}. They synthesise and release a range of hormones in the body and arise from the temporary neural crest. The term chromaffin was inspired by the staining capacity of these cells when they came into contact with chrome salts. They make, store, export and use catecholamines, responsible for making noradrenaline and originate at the caudal region of somites 18-24 of the neural crest, also known as the adrenomedullary region {{#pmid:19683477|PMID19683477}}.<br /> <br /> After splitting apart, the first neural crest cells move ventrally and pass into the spaces between the somites and then, through the anterior portions of each segment until they arrive at the para-aortic sites {{#pmid:19683477|PMID19683477}}.<br /> <br /> ===Developmental time course===<br /> ----<br /> <br /> [[File:Adrenal_Medulla_Developmental_Timeline.jpg|right|thumb|500px]]<br /> <br /> The adrenal gland has two distinct sections, the cortex and the medulla, both with different embryonic origins. The cortex accounts for 90% of the adrenal glands and arises from intermediate mesoderm. The medulla only accounts for 10% of the adult adrenal glands, however it has neural crest embryonic origin. The medulla consists of chromaffinoblast cells which are migrant neuroblast cells from the neural crest, therefore the adrenal medulla is a component of the sympathetic nervous system.{{#pmid:21175739|PMID21175739}} Neural crest cells replicate in week 7 and begin to differentiate in week 8, the cells then migrate to the developing adrenal gland in week 9 of development.{{#pmid:25255746|PMID25255746}}{{#pmid:18279781|PMID18279781}} The neural crest cells infiltrate the cortex and the chromaffin cells are scattered islands in the cortex.{{#pmid:23354096|PMID23354096}} Throughout development the cells will become more compact in the centre of the gland, during this period of development the adrenal gland is growing rapidly. The gland is abnormally large until the second trimester and the medulla is much thicker prenatally.{{#pmid:18279781|PMID18279781}}{{#pmid:21175739|PMID21175739}}<br /> <br /> ===Developmental/adult function===<br /> ----<br /> ===Tissue and Organ structure===<br /> <br /> <br /> ====Normal Structure and Function of the Adrenal Medulla====<br /> <br /> The cells of the adrenal medulla are derived from the neural crest as opposed to the mesodermal origins of the cortex. The medulla contains secretory cells called chromaffin cells, due to the agents they produce when oxidised, such as chromate. These cells secrete epinephrine and norepinephrine in response to various substances such as acetylcholine.<br /> <br /> There are three types of cells in the adult adrenal medulla: <br /> 1) Epinephrine cells<br /> <br /> 2) Norepinephrine cells <br /> <br /> 3) Small granule-containing cells (SGCs)<br /> <br /> These cells also produce various other peptides such as substance P and neurotensin. The adrenal medulla also contains presynaptic sympathetic ganglion cells. {{#pmid:1694230|PMID1694230}}<br /> <br /> ====Related Anatomy====<br /> <br /> The tissue and organ structure of the adrenal medulla should be understood with regard to its specialised function within the sympathetic nervous system. <br /> <br /> The medullary region of the adrenal glands is tasked with the endocrine secretions of adrenaline and nor-adrenaline in response to environmental stressors that are signalled for by the sympathetic nervous system. That is, the secretion of fight-or-flight response hormones in order to restrict vasculature to the trunk and increase vascular activity in the peripheral musculature.<br /> <br /> The adrenal glands are supplied by several branches of the great vessels in the abdominal cavity. The secreted catecholamines in the medulla are directly able to pass to the blood stream this way.<br /> <br /> These adrenal glands and their contents are retroperitoneal in the adult and varied in shape, with the left often being semilunar and right being pyramidal. Nervous supply of the adrenal glands is achieved by contributions from the splanchnic nerves of the celiac plexus.<br /> <br /> <br /> ====Role of the Adrenal Medulla====<br /> <br /> Understanding the biochemistry of catecholamines is necessary to see how the adrenal medulla is designed in the stages of embryology and how it is suited for life in the neonate and adult. <br /> <br /> The epinephrine and norepinephrine in the neonate and adult work by primarily changing the osmoregulatory state of vasculature in organs. With the exclusion of their neuromodulatory and neurotransmitter functions, epinephrine and norepinephrine are mainly tasked with the control of sympathetic and parasympathetic supplies. <br /> <br /> Norepinephrine is a constrictor of peripheral vasculature by antagonising the action of surface receptors expressed on the endothelium of blood vessels, specifically Alpha-1 and Alpha-2 receptors, such that vascular resistance increases. <br /> <br /> Epinephrine is both a vasoconstrictor and vasodilator, depending on what receptors it attaches to. As a non-selective adrenergic agonist, it acts on Alpha-1, Alpha-2, Beta-1, Beta-2 and Beta-3 receptors that are found throughout the body's tissues, yielding many different physiological responses.<br /> <br /> <br /> [[File:Dd.jpg|500px|thumb|right|Adult Adrenal Glands in situ]] <br /> ----<br /> <br /> ===Molecular mechanisms/factors/genes===<br /> ----<br /> <br /> ====Genes and Transcription Factors Involved with the Adrenal Medulla's Development====<br /> <br /> Members of the SOX (SRY-Box) gene family have multiple key contributors to Neural Crest in the Adrenal Medulla.<br /> <br /> Mouse models have demonstrated that SOX-10 knock-outs (mice whose DNA has been engineered to not express SOX-10) do not have an adrenal medulla. There has also been suggestion that SOX-8,9 and 10 are all strongly related to the migratory patterning of neural crest cells to the developing adrenal glands.<br /> <br /> The TH gene (for Tyrosine Hydroxylase) encodes the aforementioned enzyme in the adrenal medulla and central nervous system. Tyrosine Hydroxylase is crucial in biochemical pathways and cascades for the synthesis of catecholamines and other CNS neurotransmitters. The conversion from L-Tyrosine to L-DOPA is dependent upon the catalytic action of Tyrosine Hydroxylase. From there, L-DOPA can make Dopamine and eventually Epinephrine and Norepinephrine as well. <br /> <br /> [[File:Catecholamine_Synthesis.jpg|500px|thumb|right|Cascade of Catecholamine Synthesis]]<br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2291442/<br /> https://www.ncbi.nlm.nih.gov/pubmed/19396395<br /> <br /> ===Abnormalities/abnormal development===<br /> ----<br /> ===Animal models===<br /> ----<br /> Animal models are an integral part of research in embryology. In particular due to the moral concerns regarding the use of humans in scientific research. As a result different animals are used as substitutes to simulate the same environments and hope to achieve results that would also be able to represent humans as well. Prenatal adrenal gland development has been described in a number of scientific reports dating from the 1900s to studies in more recent years. These involved a variety of animal models such as ox, sheep, swine and most commonly mice. <br /> <br /> ====Chromaffin cells =(in rat models)====<br /> There has been extensive research conducted into the adrenal chromaffin cells and their embryological developments. As explained above nueral crest cells are pluripotent meaning they are able to differentiate into multiple different cells. The neural crest cells give rise to chromaffin cells of the adrenal medulla.<br /> <br /> To study the formation process of the adrenal medulla in the embryonic period, we visualized chromaffin cells of rat embryos at 13 to 17 days of gestation using anti-tyrosine hydroxylase (TH) antiserum, and created three-dimensional images from serial tissue sections. Between 13 and 15 days of gestation, TH-positive cells (chromaffin cells) migrated from a group of TH-positive cells present dorsal to the adrenal primordium via the medial cranial end of the adrenal primordium into the adrenal primordium. At or after 16 days of gestation, the adrenal capsule was formed except on the ventral aspect of the cranial end of the adrenal gland, from which TH-positive cells penetrated into the adrenal gland.(Pubmed: 15240937) <br /> <br /> Ahonen suggested that some neural crest cells continue migration from the chain ganglia to the lateral sides of aorta, where they form the perirenal ganglia and adrenal medulla, and finally to the ventral side of the aorta to form the preaortic sympathetic tissue. However, that report only showed the several transverse sections of the fetal trunk for the a demonstration of the migration route of neural crest cells. In this study, using three dimensional reconstructed images, we aimed to observe how TH-labeled chromaffin cells penetrate into the adrenal anlage to form the adrenal medulla and whether the migration route of TH - positive cells from the adrenal connects the preaortic sympathetic ganglia <br /> (M.Yamato, R. Yanai, K. Arishima, 2004) <br /> <br /> Prenatal adrenal gland development has been described in numerous published reports covering a wide variety of species, including the ox (Katznelson, 1966; Wrobel and Suss, 1999), sheep (Davies, 1950; Wintour et al., 1975; Upadhyay and Zamboni, 1982; Naaman‐Reperant and Durand, 1997; Grino, 2004), swine (Sokolov et al., 2006) and mouse (Waring, 1935; Ikeda et al., 1994; Sass, 1996; Nyska and Maronpot, 1999; Bland et al., 2003; Val et al., 2007). Adrenal gland development also has been extensively described for humans as well (Kolliker, 1879; Minot, 1892; Zuckerkandl, 1912; Wieman, 1920; Ikeda et al., 1981; Langlois et al., 2002; Hanley and Arit, 2006).<br /> <br /> https://www.sciencedirect.com/science/article/pii/S0925477302004550<br /> http://dev.biologists.org/content/develop/126/13/2935.full.pdf<br /> <br /> ===Current research (labs)===<br /> ----<br /> The findings presented until now have focused on the mechanisms controlling migration along the dorsolateral path. In comparison, our understanding of the mechanisms controlling NCC migration along the ventral path are complicated by the fact that this population comprises multiple precursors that form different derivatives in distinct regions of the embryo. For example, ventrally migrating NCCs either stop within the sclerotome in close association with the neural tube to form neurons and glia of the sensory nervous system (i.e. the dorsal root ganglia [DRG]), while other NCCs continue to migrate further ventrally to form the autonomic nervous system (i.e. sympathetic ganglia and chromaffin cells of the adrenal gland)<br /> <br /> Adrenomedullary chromaffin cells are catecholamine (CA)-producing cells originating from trunk neural crest (NC) via sympathoadrenal progenitors (SAPs). We generated NC and SAPs from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) in vitro via BMP2/FGF2 exposure, ascertained by qPCR and immunoexpression of SOX10, ASCL1, TFAP2α, and PHOX2B, and by fluorescence-activated cell sorting selection for p75NTR and GD2, and confirmed their trunk-like HOX gene expression. We showed that continuing BMP4 and curtailing FGF2 in vitro, augmented with corticosteroid mimetic, induced these cells to upregulate the chromaffin cell-specific marker PNMT and other CA synthesis and storage markers, and we demonstrated noradrenaline and adrenaline by Faglu and high-performance liquid chromatography. We showed these human cells' SAP-like property of migration and differentiation into cells expressing chromaffin cell markers by implanting them into avian embryos in vivo and in chorio-allantoic membrane grafts. These cells have the potential for investigating differentiation of human chromaffin cells and for modeling diseases involving this cell type.<br /> <br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768882/<br /> <br /> ===Glossary===<br /> ----<br /> ===Reference list===</div>

Z5091101 https://embryology.med.unsw.edu.au/embryology/index.php?title=2018_Group_Project_1&diff=356657 2018 Group Project 1 2018-10-10T03:26:50Z

<p>Z5091101: /* Embryonic origins */</p> <hr /> <div>=The Contribution of Neural Crest Cells to the Adrenal Medulla=<br /> ----<br /> {{2018ANAT2341ProjectHeader}}<br /> <br /> <br /> ===Introduction===<br /> [[User:Z5014972|Z5014972]] ([[User talk:Z5014972|talk]]) 12:47, 14 August 2018 (AEST)z5014972 <br /> good review article https://link.springer.com/article/10.1007%2Fs12022-009-9070-6<br /> ----<br /> <br /> <br /> The neural crest of an embryo differentiates and migrates to form various components of the body. One of these tissues is the medulla of the adrenal gland which is involved in the production of adrenalin and noradrenalin. This project will comprehensively outline the history of neural crest research, the embryonic developmental time course, tissue and organ structure, molecular mechanisms, abnormalities, animal models and current research.<br /> <br /> ===History===<br /> ----<br /> '''Describing the neural crest'''<br /> [[File:Wilhelm_His_History_Wilhelm.jpeg|left|230px|thumb|Wilhelm His]]<br /> The "neural crest" is a structure in the embryo and is the junction between the neural and epidermal ectoderm. It is exclusive to vertebrates and forms a range of structures{{#pmid:22230617|PMID22230617}}. The neural crest contributes a large number of cells of varying structure and function that directly or indirectly contribute to the development of tissues and organs within the body {{#pmid:19179766|PMID19179766}}. In 1868, the neural crest cells were first identified in a chick embryo as a collection of cells known as "Zwischenstrang" by Professor Wilhelm His {{#pmid:22820859|PMID22820859}}. Wilhelm His was among the first to provide an explanation for the mechanics governing the developing embryo as well as the physiology and the organs that the differing germinal regions would eventually give rise to. In 1878, the term neural ridge was used to describe this collection of cells but the term neural crest was later coined by Arthur Milnes Marshall in 1879 in a paper he worked on disseminating the knowledge from his research on the development of cranial nerves in chicken embryos. {{#pmid:19179766|PMID19179766}}.<br /> [[File:NC Location.jpg|left|450px|thumb|The neural crest]]<br /> <br /> '''1890s-1950s'''<br /> The neural crest is the point of origin for spinal/cranial ganglia and neurons. This theory received little criticism and was not contested much by other researchers prior to the 1890s. This is owing to the fact that the neural crest is quite closely related to the neural tube and thus this relationship makes sense. This discovery was made by His and Marshall, however, they found this out independently of one another.In the 1890s, Julia Platt, claimed that odontoblasts as well as the cartilages forming the facial and pharyngeal arch skeletons came from the ectoderm. This created much debate and was contested by many{{#pmid:22820859|PMID22820859}}. <br /> <br /> This is because this theory completely contradicted the germ-layer theory, whereby skeletal tissues originate at the mesoderm and not the ectoderm. The controversies this finding created brought about a slowing down of research, as demonstrated by a gap of almost 40 years between the theory that skeletal tissues originating from the neural crest. Today, it is known that the neural crest does indeed play a role in the development of the skeleton in vertebrates, particularly, the cranial neural crest. Although these studies were occurring, the focus was still primarily on researching pigment cells and ganglia of the spine up until the 1950s, when Sven Hörstadius' major work on the neural crest was published, titled "The Neural Crest: Its properties and derivatives in the light of experimental research". This work focused on experimental data tracing the development of the cartilaginous skeleton derived from the neural crest {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1960s - 1970s'''<br /> In the 1960s, the migration patterns of neural crest cells were studied in avian embryos (birds). This was a shift from studying the embryos of amphibians. This was inspired by studies conducted in the 1960s on neural crest cells migrating from the brain and spinal cord, known as trunk and cranial neural crest cells {{#pmid:19179766|PMID19179766}}. The cranial neural crest eventually becomes the bones, cartilage and connective tissues forming the foundation of the face, ears and teeth. The trunk neural crest cells can either become melanocytes or can migrate into sclerotomes which are later contributors to the cartilage of the spine and the dorsal root ganglia {{#pmid:22820859|PMID22820859}}. The cells in the trunk neural crest that migrate vertically become the sympathetic ganglia, the nerves proximal to the aorta and the adrenal medulla <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. In the 1970s many detailed maps signifying the pathways of many of the neural crest cells appeared as well as an understanding that the environment in which the neural crest cells are found plays a major role in their final development as well as the occurrences of abnormalities in the fetus {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1980s - 21st century'''<br /> [[File:Regions_of_NC_Cells.jpg|left|Neural crest regions|thumb]]<br /> From the 1980s-1990s, the causative agent of organ transformation from one to another (homeotic patterning), as well as the Hox genes which regulate the axis of most symmetrical animal embryos were founded and studied. The neural crest, which previously was divided into the cranial and trunk regions, was now further divided into the vagal and sacral neural crest, the cardiac neural crest and the cephalic neural crest {{#pmid:19179766|PMID19179766}}. The vagal & sacral neural crest gives rise to the parasympathetic ganglia found in the gut. Without these ganglia, peristalsis, is not possible <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. The cardiac neural crest contributes to the valves, septa and major blood vessels of the heart, as well as connective tissues and cartilage{{#pmid:19179766|PMID19179766}}. This is important for the structure of the heart as well as its overall function, enabling it to move blood around the body efficiently as well as keep pulmonary and aortic circulation separated <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> <br /> <br /> Today, knowledge of the neural crest cells, their migration patterns, modes of differentiation, derivatives and apoptosis (cell death) are being studied extensively. This is being done on a comparative basis between different organisms, to add further evidence for evolution {{#pmid:19179766|PMID19179766}}. The neural crest is definitely forging a "crest" between the fields of developmental and evolutionary biology, as it is a structure '''shared exclusively by all vertebrates'''. Invertebrates do not derive their specialised cells from the neural crest as they do not have one, rather, they derive these from the endomesoderm {{#pmid:22230617|PMID22230617}}.<br /> <br /> '''Future directions'''<br /> <br /> Since its discovery by His, the neural crest field has made great progress, from studies performed on the structure, to analysis of the molecules and whether certain aspects of the neural crest are specific to a single species of organism, or to all vertebrates collectively. Future work on the cranial neural crest needs to be done as well as identifying and categorising the networks responsible for the proliferation and death of cells, as well as how the cells move and migrate, as well as the gene regulatory networks (GRNs) that regulate the synthesis of proteins. Advances in technology will undeniable lead us to more answers on the subject {{#pmid:22230617|PMID22230617}}.<br /> <br /> ===Embryonic origins===<br /> ----<br /> https://www.ncbi.nlm.nih.gov/books/NBK10065/<br /> <br /> The adrenal gland is made up of the adrenal cortex and adrenal medulla, which both have different embryonic origins. The adrenal medulla arises from the neural crest tissue, found near the level of the coeliac plexus & sympathetic ganglion at somites 18-24 {{#pmid:16124976|PMID16124976}}. Specifically, this neural crest tissue comes from the trunk neural crest cells (see above figure to determine the approximate location in an embryo) <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> The trunk neural crest coordinates the development of the endocrine system, secretory cells, the peripheral nervous system and, to some degree, skeletal development, as well as innervation of the intestine {{#pmid: 28287247|PMID 28287247}}. The trunk neural cells arise caudally, undergo an epithelial to mesenchymal transition and follow three migratory pathways {{#pmid:20399766|PMID20399766}}.<br /> <br /> - '''A dorsolateral pathway''' (between ectoderm and somites), these become melanocytes, travel up to the point of the dermis and become a major part of the hair follicles and skin <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> - A ventrolateral pathway (through the somites)<br /> - A ventromedial pathway (between neural tube and posterior schlerotome){{#pmid:20399766|PMID20399766}}.<br /> <br /> Migration of neural crest cells from the sympathetic ganglion is what leads to the development of the adrenal medulla. In week 8 of development, immature cells called neuroblasts migrate through to the inner portion of the medulla, where they become the adrenal medulla {{#pmid:16392182|PMID16392182}}. Chromaffin cells are neuroendocrine cells and are found in the sympathetic ganglia and make up the majority of the adrenal medulla{{#pmid:16392182|PMID16392182}}. They synthesise and release a range of hormones in the body and arise from the temporary neural crest. The term chromaffin was inspired by the staining capacity of these cells when they came into contact with chrome salts. They make, store, export and use catecholamines, responsible for making noradrenaline and originate at the caudal region of somites 18-24 of the neural crest, also known as the adrenomedullary region {{#pmid:16392182|PMID16392182}}.<br /> <br /> After splitting apart, the first neural crest cells move ventrally and pass into the spaces between the somites and then, through the anterior portions of each segment until they arrive at the para-aortic sites {{#pmid:16392182|PMID16392182}}.<br /> <br /> ===Developmental time course===<br /> ----<br /> <br /> [[File:Adrenal_Medulla_Developmental_Timeline.jpg|right|thumb|500px]]<br /> <br /> The adrenal gland has two distinct sections, the cortex and the medulla, both with different embryonic origins. The cortex accounts for 90% of the adrenal glands and arises from intermediate mesoderm. The medulla only accounts for 10% of the adult adrenal glands, however it has neural crest embryonic origin. The medulla consists of chromaffinoblast cells which are migrant neuroblast cells from the neural crest, therefore the adrenal medulla is a component of the sympathetic nervous system.{{#pmid:21175739|PMID21175739}} Neural crest cells replicate in week 7 and begin to differentiate in week 8, the cells then migrate to the developing adrenal gland in week 9 of development.{{#pmid:25255746|PMID25255746}}{{#pmid:18279781|PMID18279781}} The neural crest cells infiltrate the cortex and the chromaffin cells are scattered islands in the cortex.{{#pmid:23354096|PMID23354096}} Throughout development the cells will become more compact in the centre of the gland, during this period of development the adrenal gland is growing rapidly. The gland is abnormally large until the second trimester and the medulla is much thicker prenatally.{{#pmid:18279781|PMID18279781}}{{#pmid:21175739|PMID21175739}}<br /> <br /> ===Developmental/adult function===<br /> ----<br /> ===Tissue and Organ structure===<br /> <br /> <br /> ====Normal Structure and Function of the Adrenal Medulla====<br /> <br /> The cells of the adrenal medulla are derived from the neural crest as opposed to the mesodermal origins of the cortex. The medulla contains secretory cells called chromaffin cells, due to the agents they produce when oxidised, such as chromate. These cells secrete epinephrine and norepinephrine in response to various substances such as acetylcholine.<br /> <br /> There are three types of cells in the adult adrenal medulla: <br /> 1) Epinephrine cells<br /> <br /> 2) Norepinephrine cells <br /> <br /> 3) Small granule-containing cells (SGCs)<br /> <br /> These cells also produce various other peptides such as substance P and neurotensin. The adrenal medulla also contains presynaptic sympathetic ganglion cells. {{#pmid:1694230|PMID1694230}}<br /> <br /> ====Related Anatomy====<br /> <br /> The tissue and organ structure of the adrenal medulla should be understood with regard to its specialised function within the sympathetic nervous system. <br /> <br /> The medullary region of the adrenal glands is tasked with the endocrine secretions of adrenaline and nor-adrenaline in response to environmental stressors that are signalled for by the sympathetic nervous system. That is, the secretion of fight-or-flight response hormones in order to restrict vasculature to the trunk and increase vascular activity in the peripheral musculature.<br /> <br /> The adrenal glands are supplied by several branches of the great vessels in the abdominal cavity. The secreted catecholamines in the medulla are directly able to pass to the blood stream this way.<br /> <br /> These adrenal glands and their contents are retroperitoneal in the adult and varied in shape, with the left often being semilunar and right being pyramidal. Nervous supply of the adrenal glands is achieved by contributions from the splanchnic nerves of the celiac plexus.<br /> <br /> <br /> ====Role of the Adrenal Medulla====<br /> <br /> Understanding the biochemistry of catecholamines is necessary to see how the adrenal medulla is designed in the stages of embryology and how it is suited for life in the neonate and adult. <br /> <br /> The epinephrine and norepinephrine in the neonate and adult work by primarily changing the osmoregulatory state of vasculature in organs. With the exclusion of their neuromodulatory and neurotransmitter functions, epinephrine and norepinephrine are mainly tasked with the control of sympathetic and parasympathetic supplies. <br /> <br /> Norepinephrine is a constrictor of peripheral vasculature by antagonising the action of surface receptors expressed on the endothelium of blood vessels, specifically Alpha-1 and Alpha-2 receptors, such that vascular resistance increases. <br /> <br /> Epinephrine is both a vasoconstrictor and vasodilator, depending on what receptors it attaches to. As a non-selective adrenergic agonist, it acts on Alpha-1, Alpha-2, Beta-1, Beta-2 and Beta-3 receptors that are found throughout the body's tissues, yielding many different physiological responses.<br /> <br /> <br /> [[File:Dd.jpg|500px|thumb|right|Adult Adrenal Glands in situ]] <br /> ----<br /> <br /> ===Molecular mechanisms/factors/genes===<br /> ----<br /> <br /> ====Genes and Transcription Factors Involved with the Adrenal Medulla's Development====<br /> <br /> Members of the SOX (SRY-Box) gene family have multiple key contributors to Neural Crest in the Adrenal Medulla.<br /> <br /> Mouse models have demonstrated that SOX-10 knock-outs (mice whose DNA has been engineered to not express SOX-10) do not have an adrenal medulla. There has also been suggestion that SOX-8,9 and 10 are all strongly related to the migratory patterning of neural crest cells to the developing adrenal glands.<br /> <br /> The TH gene (for Tyrosine Hydroxylase) encodes the aforementioned enzyme in the adrenal medulla and central nervous system. Tyrosine Hydroxylase is crucial in biochemical pathways and cascades for the synthesis of catecholamines and other CNS neurotransmitters. The conversion from L-Tyrosine to L-DOPA is dependent upon the catalytic action of Tyrosine Hydroxylase. From there, L-DOPA can make Dopamine and eventually Epinephrine and Norepinephrine as well. <br /> <br /> [[File:Catecholamine_Synthesis.jpg|500px|thumb|right|Cascade of Catecholamine Synthesis]]<br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2291442/<br /> https://www.ncbi.nlm.nih.gov/pubmed/19396395<br /> <br /> ===Abnormalities/abnormal development===<br /> ----<br /> ===Animal models===<br /> ----<br /> Animal models are an integral part of research in embryology. In particular due to the moral concerns regarding the use of humans in scientific research. As a result different animals are used as substitutes to simulate the same environments and hope to achieve results that would also be able to represent humans as well. Prenatal adrenal gland development has been described in a number of scientific reports dating from the 1900s to studies in more recent years. These involved a variety of animal models such as ox, sheep, swine and most commonly mice. <br /> <br /> ====Chromaffin cells =(in rat models)====<br /> There has been extensive research conducted into the adrenal chromaffin cells and their embryological developments. As explained above nueral crest cells are pluripotent meaning they are able to differentiate into multiple different cells. The neural crest cells give rise to chromaffin cells of the adrenal medulla.<br /> <br /> To study the formation process of the adrenal medulla in the embryonic period, we visualized chromaffin cells of rat embryos at 13 to 17 days of gestation using anti-tyrosine hydroxylase (TH) antiserum, and created three-dimensional images from serial tissue sections. Between 13 and 15 days of gestation, TH-positive cells (chromaffin cells) migrated from a group of TH-positive cells present dorsal to the adrenal primordium via the medial cranial end of the adrenal primordium into the adrenal primordium. At or after 16 days of gestation, the adrenal capsule was formed except on the ventral aspect of the cranial end of the adrenal gland, from which TH-positive cells penetrated into the adrenal gland.(Pubmed: 15240937) <br /> <br /> Ahonen suggested that some neural crest cells continue migration from the chain ganglia to the lateral sides of aorta, where they form the perirenal ganglia and adrenal medulla, and finally to the ventral side of the aorta to form the preaortic sympathetic tissue. However, that report only showed the several transverse sections of the fetal trunk for the a demonstration of the migration route of neural crest cells. In this study, using three dimensional reconstructed images, we aimed to observe how TH-labeled chromaffin cells penetrate into the adrenal anlage to form the adrenal medulla and whether the migration route of TH - positive cells from the adrenal connects the preaortic sympathetic ganglia <br /> (M.Yamato, R. Yanai, K. Arishima, 2004) <br /> <br /> Prenatal adrenal gland development has been described in numerous published reports covering a wide variety of species, including the ox (Katznelson, 1966; Wrobel and Suss, 1999), sheep (Davies, 1950; Wintour et al., 1975; Upadhyay and Zamboni, 1982; Naaman‐Reperant and Durand, 1997; Grino, 2004), swine (Sokolov et al., 2006) and mouse (Waring, 1935; Ikeda et al., 1994; Sass, 1996; Nyska and Maronpot, 1999; Bland et al., 2003; Val et al., 2007). Adrenal gland development also has been extensively described for humans as well (Kolliker, 1879; Minot, 1892; Zuckerkandl, 1912; Wieman, 1920; Ikeda et al., 1981; Langlois et al., 2002; Hanley and Arit, 2006).<br /> <br /> https://www.sciencedirect.com/science/article/pii/S0925477302004550<br /> http://dev.biologists.org/content/develop/126/13/2935.full.pdf<br /> <br /> ===Current research (labs)===<br /> ----<br /> The findings presented until now have focused on the mechanisms controlling migration along the dorsolateral path. In comparison, our understanding of the mechanisms controlling NCC migration along the ventral path are complicated by the fact that this population comprises multiple precursors that form different derivatives in distinct regions of the embryo. For example, ventrally migrating NCCs either stop within the sclerotome in close association with the neural tube to form neurons and glia of the sensory nervous system (i.e. the dorsal root ganglia [DRG]), while other NCCs continue to migrate further ventrally to form the autonomic nervous system (i.e. sympathetic ganglia and chromaffin cells of the adrenal gland)<br /> <br /> Adrenomedullary chromaffin cells are catecholamine (CA)-producing cells originating from trunk neural crest (NC) via sympathoadrenal progenitors (SAPs). We generated NC and SAPs from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) in vitro via BMP2/FGF2 exposure, ascertained by qPCR and immunoexpression of SOX10, ASCL1, TFAP2α, and PHOX2B, and by fluorescence-activated cell sorting selection for p75NTR and GD2, and confirmed their trunk-like HOX gene expression. We showed that continuing BMP4 and curtailing FGF2 in vitro, augmented with corticosteroid mimetic, induced these cells to upregulate the chromaffin cell-specific marker PNMT and other CA synthesis and storage markers, and we demonstrated noradrenaline and adrenaline by Faglu and high-performance liquid chromatography. We showed these human cells' SAP-like property of migration and differentiation into cells expressing chromaffin cell markers by implanting them into avian embryos in vivo and in chorio-allantoic membrane grafts. These cells have the potential for investigating differentiation of human chromaffin cells and for modeling diseases involving this cell type.<br /> <br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768882/<br /> <br /> ===Glossary===<br /> ----<br /> ===Reference list===</div>

Z5091101 https://embryology.med.unsw.edu.au/embryology/index.php?title=2018_Group_Project_1&diff=356655 2018 Group Project 1 2018-10-10T02:33:40Z

<p>Z5091101: /* Embryonic origins */</p> <hr /> <div>=The Contribution of Neural Crest Cells to the Adrenal Medulla=<br /> ----<br /> {{2018ANAT2341ProjectHeader}}<br /> <br /> <br /> ===Introduction===<br /> [[User:Z5014972|Z5014972]] ([[User talk:Z5014972|talk]]) 12:47, 14 August 2018 (AEST)z5014972 <br /> good review article https://link.springer.com/article/10.1007%2Fs12022-009-9070-6<br /> ----<br /> <br /> <br /> The neural crest of an embryo differentiates and migrates to form various components of the body. One of these tissues is the medulla of the adrenal gland which is involved in the production of adrenalin and noradrenalin. This project will comprehensively outline the history of neural crest research, the embryonic developmental time course, tissue and organ structure, molecular mechanisms, abnormalities, animal models and current research.<br /> <br /> ===History===<br /> ----<br /> '''Describing the neural crest'''<br /> [[File:Wilhelm_His_History_Wilhelm.jpeg|left|230px|thumb|Wilhelm His]]<br /> The "neural crest" is a structure in the embryo and is the junction between the neural and epidermal ectoderm. It is exclusive to vertebrates and forms a range of structures{{#pmid:22230617|PMID22230617}}. The neural crest contributes a large number of cells of varying structure and function that directly or indirectly contribute to the development of tissues and organs within the body {{#pmid:19179766|PMID19179766}}. In 1868, the neural crest cells were first identified in a chick embryo as a collection of cells known as "Zwischenstrang" by Professor Wilhelm His {{#pmid:22820859|PMID22820859}}. Wilhelm His was among the first to provide an explanation for the mechanics governing the developing embryo as well as the physiology and the organs that the differing germinal regions would eventually give rise to. In 1878, the term neural ridge was used to describe this collection of cells but the term neural crest was later coined by Arthur Milnes Marshall in 1879 in a paper he worked on disseminating the knowledge from his research on the development of cranial nerves in chicken embryos. {{#pmid:19179766|PMID19179766}}.<br /> [[File:NC Location.jpg|left|450px|thumb|The neural crest]]<br /> <br /> '''1890s-1950s'''<br /> The neural crest is the point of origin for spinal/cranial ganglia and neurons. This theory received little criticism and was not contested much by other researchers prior to the 1890s. This is owing to the fact that the neural crest is quite closely related to the neural tube and thus this relationship makes sense. This discovery was made by His and Marshall, however, they found this out independently of one another.In the 1890s, Julia Platt, claimed that odontoblasts as well as the cartilages forming the facial and pharyngeal arch skeletons came from the ectoderm. This created much debate and was contested by many{{#pmid:22820859|PMID22820859}}. <br /> <br /> This is because this theory completely contradicted the germ-layer theory, whereby skeletal tissues originate at the mesoderm and not the ectoderm. The controversies this finding created brought about a slowing down of research, as demonstrated by a gap of almost 40 years between the theory that skeletal tissues originating from the neural crest. Today, it is known that the neural crest does indeed play a role in the development of the skeleton in vertebrates, particularly, the cranial neural crest. Although these studies were occurring, the focus was still primarily on researching pigment cells and ganglia of the spine up until the 1950s, when Sven Hörstadius' major work on the neural crest was published, titled "The Neural Crest: Its properties and derivatives in the light of experimental research". This work focused on experimental data tracing the development of the cartilaginous skeleton derived from the neural crest {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1960s - 1970s'''<br /> In the 1960s, the migration patterns of neural crest cells were studied in avian embryos (birds). This was a shift from studying the embryos of amphibians. This was inspired by studies conducted in the 1960s on neural crest cells migrating from the brain and spinal cord, known as trunk and cranial neural crest cells {{#pmid:19179766|PMID19179766}}. The cranial neural crest eventually becomes the bones, cartilage and connective tissues forming the foundation of the face, ears and teeth. The trunk neural crest cells can either become melanocytes or can migrate into sclerotomes which are later contributors to the cartilage of the spine and the dorsal root ganglia {{#pmid:22820859|PMID22820859}}. The cells in the trunk neural crest that migrate vertically become the sympathetic ganglia, the nerves proximal to the aorta and the adrenal medulla <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. In the 1970s many detailed maps signifying the pathways of many of the neural crest cells appeared as well as an understanding that the environment in which the neural crest cells are found plays a major role in their final development as well as the occurrences of abnormalities in the fetus {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1980s - 21st century'''<br /> [[File:Regions_of_NC_Cells.jpg|left|Neural crest regions|thumb]]<br /> From the 1980s-1990s, the causative agent of organ transformation from one to another (homeotic patterning), as well as the Hox genes which regulate the axis of most symmetrical animal embryos were founded and studied. The neural crest, which previously was divided into the cranial and trunk regions, was now further divided into the vagal and sacral neural crest, the cardiac neural crest and the cephalic neural crest {{#pmid:19179766|PMID19179766}}. The vagal & sacral neural crest gives rise to the parasympathetic ganglia found in the gut. Without these ganglia, peristalsis, is not possible <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. The cardiac neural crest contributes to the valves, septa and major blood vessels of the heart, as well as connective tissues and cartilage{{#pmid:19179766|PMID19179766}}. This is important for the structure of the heart as well as its overall function, enabling it to move blood around the body efficiently as well as keep pulmonary and aortic circulation separated <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> <br /> <br /> Today, knowledge of the neural crest cells, their migration patterns, modes of differentiation, derivatives and apoptosis (cell death) are being studied extensively. This is being done on a comparative basis between different organisms, to add further evidence for evolution {{#pmid:19179766|PMID19179766}}. The neural crest is definitely forging a "crest" between the fields of developmental and evolutionary biology, as it is a structure '''shared exclusively by all vertebrates'''. Invertebrates do not derive their specialised cells from the neural crest as they do not have one, rather, they derive these from the endomesoderm {{#pmid:22230617|PMID22230617}}.<br /> <br /> '''Future directions'''<br /> <br /> Since its discovery by His, the neural crest field has made great progress, from studies performed on the structure, to analysis of the molecules and whether certain aspects of the neural crest are specific to a single species of organism, or to all vertebrates collectively. Future work on the cranial neural crest needs to be done as well as identifying and categorising the networks responsible for the proliferation and death of cells, as well as how the cells move and migrate, as well as the gene regulatory networks (GRNs) that regulate the synthesis of proteins. Advances in technology will undeniable lead us to more answers on the subject {{#pmid:22230617|PMID22230617}}.<br /> <br /> ===Embryonic origins===<br /> ----<br /> https://www.ncbi.nlm.nih.gov/books/NBK10065/<br /> <br /> The adrenal gland is made up of the adrenal cortex and adrenal medulla, which both have different embryonic origins. The adrenal medulla arises from the neural crest tissue, found near the level of the coeliac plexus & sympathetic ganglion at somites 18-24 {{#pmid:16124976|PMID16124976}}. Specifically, this neural crest tissue comes from the trunk neural crest cells (see above figure to determine the approximate location in an embryo) <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> The trunk neural crest coordinates the development of the endocrine system, secretory cells, the peripheral nervous system and, to some degree, skeletal development, as well as innervation of the intestine {{#pmid: 28287247|PMID 28287247}}. The trunk neural cells arise caudally and follow three migratory pathways {{#pmid:20399766|PMID20399766}}.<br /> <br /> - A dorsolateral pathway (between ectoderm and somites)<br /> - A ventrolateral pathway (through the somites)<br /> - A ventromedial pathway (between neural tube and posterior schlerotome){{#pmid:20399766|PMID20399766}}.<br /> <br /> Migration of neural crest cells from the sympathetic ganglion is what leads to the development of the adrenal medulla. In week 8 of development, immature cells called neuroblasts migrate through to the inner portion of the medulla, where they become the adrenal medulla {{#pmid:16392182|PMID16392182}}.<br /> <br /> ===Developmental time course===<br /> ----<br /> <br /> [[File:Adrenal_Medulla_Developmental_Timeline.jpg|right|thumb|500px]]<br /> <br /> The adrenal gland has two distinct sections, the cortex and the medulla, both with different embryonic origins. The cortex accounts for 90% of the adrenal glands and arises from intermediate mesoderm. The medulla only accounts for 10% of the adult adrenal glands, however it has neural crest embryonic origin. The medulla consists of chromaffinoblast cells which are migrant neuroblast cells from the neural crest, therefore the adrenal medulla is a component of the sympathetic nervous system.{{#pmid:21175739|PMID21175739}} Neural crest cells replicate in week 7 and begin to differentiate in week 8, the cells then migrate to the developing adrenal gland in week 9 of development.{{#pmid:25255746|PMID25255746}}{{#pmid:18279781|PMID18279781}} The neural crest cells infiltrate the cortex and the chromaffin cells are scattered islands in the cortex.{{#pmid:23354096|PMID23354096}} Throughout development the cells will become more compact in the centre of the gland, during this period of development the adrenal gland is growing rapidly. The gland is abnormally large until the second trimester and the medulla is much thicker prenatally.{{#pmid:18279781|PMID18279781}}{{#pmid:21175739|PMID21175739}}<br /> <br /> ===Developmental/adult function===<br /> ----<br /> ===Tissue and Organ structure===<br /> <br /> <br /> ====Normal Structure and Function of the Adrenal Medulla====<br /> <br /> The cells of the adrenal medulla are derived from the neural crest as opposed to the mesodermal origins of the cortex. The medulla contains secretory cells called chromaffin cells, due to the agents they produce when oxidised, such as chromate. These cells secrete epinephrine and norepinephrine in response to various substances such as acetylcholine.<br /> <br /> There are three types of cells in the adult adrenal medulla: <br /> 1) Epinephrine cells<br /> <br /> 2) Norepinephrine cells <br /> <br /> 3) Small granule-containing cells (SGCs)<br /> <br /> These cells also produce various other peptides such as substance P and neurotensin. The adrenal medulla also contains presynaptic sympathetic ganglion cells. {{#pmid:1694230|PMID1694230}}<br /> <br /> ====Related Anatomy====<br /> <br /> The tissue and organ structure of the adrenal medulla should be understood with regard to its specialised function within the sympathetic nervous system. <br /> <br /> The medullary region of the adrenal glands is tasked with the endocrine secretions of adrenaline and nor-adrenaline in response to environmental stressors that are signalled for by the sympathetic nervous system. That is, the secretion of fight-or-flight response hormones in order to restrict vasculature to the trunk and increase vascular activity in the peripheral musculature.<br /> <br /> The adrenal glands are supplied by several branches of the great vessels in the abdominal cavity. The secreted catecholamines in the medulla are directly able to pass to the blood stream this way.<br /> <br /> These adrenal glands and their contents are retroperitoneal in the adult and varied in shape, with the left often being semilunar and right being pyramidal. Nervous supply of the adrenal glands is achieved by contributions from the splanchnic nerves of the celiac plexus.<br /> <br /> <br /> ====Role of the Adrenal Medulla====<br /> <br /> Understanding the biochemistry of catecholamines is necessary to see how the adrenal medulla is designed in the stages of embryology and how it is suited for life in the neonate and adult. <br /> <br /> The epinephrine and norepinephrine in the neonate and adult work by primarily changing the osmoregulatory state of vasculature in organs. With the exclusion of their neuromodulatory and neurotransmitter functions, epinephrine and norepinephrine are mainly tasked with the control of sympathetic and parasympathetic supplies. <br /> <br /> Norepinephrine is a constrictor of peripheral vasculature by antagonising the action of surface receptors expressed on the endothelium of blood vessels, specifically Alpha-1 and Alpha-2 receptors, such that vascular resistance increases. <br /> <br /> Epinephrine is both a vasoconstrictor and vasodilator, depending on what receptors it attaches to. As a non-selective adrenergic agonist, it acts on Alpha-1, Alpha-2, Beta-1, Beta-2 and Beta-3 receptors that are found throughout the body's tissues, yielding many different physiological responses.<br /> <br /> <br /> [[File:Dd.jpg|500px|thumb|right|Adult Adrenal Glands in situ]] <br /> ----<br /> <br /> ===Molecular mechanisms/factors/genes===<br /> ----<br /> <br /> ====Genes and Transcription Factors Involved with the Adrenal Medulla's Development====<br /> <br /> Members of the SOX (SRY-Box) gene family have multiple key contributors to Neural Crest in the Adrenal Medulla.<br /> <br /> Mouse models have demonstrated that SOX-10 knock-outs (mice whose DNA has been engineered to not express SOX-10) do not have an adrenal medulla. There has also been suggestion that SOX-8,9 and 10 are all strongly related to the migratory patterning of neural crest cells to the developing adrenal glands.<br /> <br /> The TH gene (for Tyrosine Hydroxylase) encodes the aforementioned enzyme in the adrenal medulla and central nervous system. Tyrosine Hydroxylase is crucial in biochemical pathways and cascades for the synthesis of catecholamines and other CNS neurotransmitters. The conversion from L-Tyrosine to L-DOPA is dependent upon the catalytic action of Tyrosine Hydroxylase. From there, L-DOPA can make Dopamine and eventually Epinephrine and Norepinephrine as well. <br /> <br /> [[File:Catecholamine_Synthesis.jpg|500px|thumb|right|Cascade of Catecholamine Synthesis]]<br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2291442/<br /> https://www.ncbi.nlm.nih.gov/pubmed/19396395<br /> <br /> ===Abnormalities/abnormal development===<br /> ----<br /> ===Animal models===<br /> ----<br /> Animal models are an integral part of research in embryology. In particular due to the moral concerns regarding the use of humans in scientific research. As a result different animals are used as substitutes to simulate the same environments and hope to achieve results that would also be able to represent humans as well. Prenatal adrenal gland development has been described in a number of scientific reports dating from the 1900s to studies in more recent years. These involved a variety of animal models such as ox, sheep, swine and most commonly mice. <br /> <br /> ====Chromaffin cells =(in rat models)====<br /> There has been extensive research conducted into the adrenal chromaffin cells and their embryological developments. As explained above nueral crest cells are pluripotent meaning they are able to differentiate into multiple different cells. The neural crest cells give rise to chromaffin cells of the adrenal medulla.<br /> <br /> To study the formation process of the adrenal medulla in the embryonic period, we visualized chromaffin cells of rat embryos at 13 to 17 days of gestation using anti-tyrosine hydroxylase (TH) antiserum, and created three-dimensional images from serial tissue sections. Between 13 and 15 days of gestation, TH-positive cells (chromaffin cells) migrated from a group of TH-positive cells present dorsal to the adrenal primordium via the medial cranial end of the adrenal primordium into the adrenal primordium. At or after 16 days of gestation, the adrenal capsule was formed except on the ventral aspect of the cranial end of the adrenal gland, from which TH-positive cells penetrated into the adrenal gland.(Pubmed: 15240937) <br /> <br /> Ahonen suggested that some neural crest cells continue migration from the chain ganglia to the lateral sides of aorta, where they form the perirenal ganglia and adrenal medulla, and finally to the ventral side of the aorta to form the preaortic sympathetic tissue. However, that report only showed the several transverse sections of the fetal trunk for the a demonstration of the migration route of neural crest cells. In this study, using three dimensional reconstructed images, we aimed to observe how TH-labeled chromaffin cells penetrate into the adrenal anlage to form the adrenal medulla and whether the migration route of TH - positive cells from the adrenal connects the preaortic sympathetic ganglia <br /> (M.Yamato, R. Yanai, K. Arishima, 2004) <br /> <br /> Prenatal adrenal gland development has been described in numerous published reports covering a wide variety of species, including the ox (Katznelson, 1966; Wrobel and Suss, 1999), sheep (Davies, 1950; Wintour et al., 1975; Upadhyay and Zamboni, 1982; Naaman‐Reperant and Durand, 1997; Grino, 2004), swine (Sokolov et al., 2006) and mouse (Waring, 1935; Ikeda et al., 1994; Sass, 1996; Nyska and Maronpot, 1999; Bland et al., 2003; Val et al., 2007). Adrenal gland development also has been extensively described for humans as well (Kolliker, 1879; Minot, 1892; Zuckerkandl, 1912; Wieman, 1920; Ikeda et al., 1981; Langlois et al., 2002; Hanley and Arit, 2006).<br /> <br /> https://www.sciencedirect.com/science/article/pii/S0925477302004550<br /> http://dev.biologists.org/content/develop/126/13/2935.full.pdf<br /> <br /> ===Current research (labs)===<br /> ----<br /> The findings presented until now have focused on the mechanisms controlling migration along the dorsolateral path. In comparison, our understanding of the mechanisms controlling NCC migration along the ventral path are complicated by the fact that this population comprises multiple precursors that form different derivatives in distinct regions of the embryo. For example, ventrally migrating NCCs either stop within the sclerotome in close association with the neural tube to form neurons and glia of the sensory nervous system (i.e. the dorsal root ganglia [DRG]), while other NCCs continue to migrate further ventrally to form the autonomic nervous system (i.e. sympathetic ganglia and chromaffin cells of the adrenal gland)<br /> <br /> Adrenomedullary chromaffin cells are catecholamine (CA)-producing cells originating from trunk neural crest (NC) via sympathoadrenal progenitors (SAPs). We generated NC and SAPs from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) in vitro via BMP2/FGF2 exposure, ascertained by qPCR and immunoexpression of SOX10, ASCL1, TFAP2α, and PHOX2B, and by fluorescence-activated cell sorting selection for p75NTR and GD2, and confirmed their trunk-like HOX gene expression. We showed that continuing BMP4 and curtailing FGF2 in vitro, augmented with corticosteroid mimetic, induced these cells to upregulate the chromaffin cell-specific marker PNMT and other CA synthesis and storage markers, and we demonstrated noradrenaline and adrenaline by Faglu and high-performance liquid chromatography. We showed these human cells' SAP-like property of migration and differentiation into cells expressing chromaffin cell markers by implanting them into avian embryos in vivo and in chorio-allantoic membrane grafts. These cells have the potential for investigating differentiation of human chromaffin cells and for modeling diseases involving this cell type.<br /> <br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768882/<br /> <br /> ===Glossary===<br /> ----<br /> ===Reference list===</div>

Z5091101 https://embryology.med.unsw.edu.au/embryology/index.php?title=2018_Group_Project_1&diff=356653 2018 Group Project 1 2018-10-10T02:29:53Z

<p>Z5091101: /* Embryonic origins */</p> <hr /> <div>=The Contribution of Neural Crest Cells to the Adrenal Medulla=<br /> ----<br /> {{2018ANAT2341ProjectHeader}}<br /> <br /> <br /> ===Introduction===<br /> [[User:Z5014972|Z5014972]] ([[User talk:Z5014972|talk]]) 12:47, 14 August 2018 (AEST)z5014972 <br /> good review article https://link.springer.com/article/10.1007%2Fs12022-009-9070-6<br /> ----<br /> <br /> <br /> The neural crest of an embryo differentiates and migrates to form various components of the body. One of these tissues is the medulla of the adrenal gland which is involved in the production of adrenalin and noradrenalin. This project will comprehensively outline the history of neural crest research, the embryonic developmental time course, tissue and organ structure, molecular mechanisms, abnormalities, animal models and current research.<br /> <br /> ===History===<br /> ----<br /> '''Describing the neural crest'''<br /> [[File:Wilhelm_His_History_Wilhelm.jpeg|left|230px|thumb|Wilhelm His]]<br /> The "neural crest" is a structure in the embryo and is the junction between the neural and epidermal ectoderm. It is exclusive to vertebrates and forms a range of structures{{#pmid:22230617|PMID22230617}}. The neural crest contributes a large number of cells of varying structure and function that directly or indirectly contribute to the development of tissues and organs within the body {{#pmid:19179766|PMID19179766}}. In 1868, the neural crest cells were first identified in a chick embryo as a collection of cells known as "Zwischenstrang" by Professor Wilhelm His {{#pmid:22820859|PMID22820859}}. Wilhelm His was among the first to provide an explanation for the mechanics governing the developing embryo as well as the physiology and the organs that the differing germinal regions would eventually give rise to. In 1878, the term neural ridge was used to describe this collection of cells but the term neural crest was later coined by Arthur Milnes Marshall in 1879 in a paper he worked on disseminating the knowledge from his research on the development of cranial nerves in chicken embryos. {{#pmid:19179766|PMID19179766}}.<br /> [[File:NC Location.jpg|left|450px|thumb|The neural crest]]<br /> <br /> '''1890s-1950s'''<br /> The neural crest is the point of origin for spinal/cranial ganglia and neurons. This theory received little criticism and was not contested much by other researchers prior to the 1890s. This is owing to the fact that the neural crest is quite closely related to the neural tube and thus this relationship makes sense. This discovery was made by His and Marshall, however, they found this out independently of one another.In the 1890s, Julia Platt, claimed that odontoblasts as well as the cartilages forming the facial and pharyngeal arch skeletons came from the ectoderm. This created much debate and was contested by many{{#pmid:22820859|PMID22820859}}. <br /> <br /> This is because this theory completely contradicted the germ-layer theory, whereby skeletal tissues originate at the mesoderm and not the ectoderm. The controversies this finding created brought about a slowing down of research, as demonstrated by a gap of almost 40 years between the theory that skeletal tissues originating from the neural crest. Today, it is known that the neural crest does indeed play a role in the development of the skeleton in vertebrates, particularly, the cranial neural crest. Although these studies were occurring, the focus was still primarily on researching pigment cells and ganglia of the spine up until the 1950s, when Sven Hörstadius' major work on the neural crest was published, titled "The Neural Crest: Its properties and derivatives in the light of experimental research". This work focused on experimental data tracing the development of the cartilaginous skeleton derived from the neural crest {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1960s - 1970s'''<br /> In the 1960s, the migration patterns of neural crest cells were studied in avian embryos (birds). This was a shift from studying the embryos of amphibians. This was inspired by studies conducted in the 1960s on neural crest cells migrating from the brain and spinal cord, known as trunk and cranial neural crest cells {{#pmid:19179766|PMID19179766}}. The cranial neural crest eventually becomes the bones, cartilage and connective tissues forming the foundation of the face, ears and teeth. The trunk neural crest cells can either become melanocytes or can migrate into sclerotomes which are later contributors to the cartilage of the spine and the dorsal root ganglia {{#pmid:22820859|PMID22820859}}. The cells in the trunk neural crest that migrate vertically become the sympathetic ganglia, the nerves proximal to the aorta and the adrenal medulla <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. In the 1970s many detailed maps signifying the pathways of many of the neural crest cells appeared as well as an understanding that the environment in which the neural crest cells are found plays a major role in their final development as well as the occurrences of abnormalities in the fetus {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1980s - 21st century'''<br /> [[File:Regions_of_NC_Cells.jpg|left|Neural crest regions|thumb]]<br /> From the 1980s-1990s, the causative agent of organ transformation from one to another (homeotic patterning), as well as the Hox genes which regulate the axis of most symmetrical animal embryos were founded and studied. The neural crest, which previously was divided into the cranial and trunk regions, was now further divided into the vagal and sacral neural crest, the cardiac neural crest and the cephalic neural crest {{#pmid:19179766|PMID19179766}}. The vagal & sacral neural crest gives rise to the parasympathetic ganglia found in the gut. Without these ganglia, peristalsis, is not possible <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. The cardiac neural crest contributes to the valves, septa and major blood vessels of the heart, as well as connective tissues and cartilage{{#pmid:19179766|PMID19179766}}. This is important for the structure of the heart as well as its overall function, enabling it to move blood around the body efficiently as well as keep pulmonary and aortic circulation separated <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> <br /> <br /> Today, knowledge of the neural crest cells, their migration patterns, modes of differentiation, derivatives and apoptosis (cell death) are being studied extensively. This is being done on a comparative basis between different organisms, to add further evidence for evolution {{#pmid:19179766|PMID19179766}}. The neural crest is definitely forging a "crest" between the fields of developmental and evolutionary biology, as it is a structure '''shared exclusively by all vertebrates'''. Invertebrates do not derive their specialised cells from the neural crest as they do not have one, rather, they derive these from the endomesoderm {{#pmid:22230617|PMID22230617}}.<br /> <br /> '''Future directions'''<br /> <br /> Since its discovery by His, the neural crest field has made great progress, from studies performed on the structure, to analysis of the molecules and whether certain aspects of the neural crest are specific to a single species of organism, or to all vertebrates collectively. Future work on the cranial neural crest needs to be done as well as identifying and categorising the networks responsible for the proliferation and death of cells, as well as how the cells move and migrate, as well as the gene regulatory networks (GRNs) that regulate the synthesis of proteins. Advances in technology will undeniable lead us to more answers on the subject {{#pmid:22230617|PMID22230617}}.<br /> <br /> ===Embryonic origins===<br /> ----<br /> https://www.ncbi.nlm.nih.gov/books/NBK10065/<br /> <br /> The adrenal gland is made up of the adrenal cortex and adrenal medulla, which both have different embryonic origins. The adrenal medulla arises from the neural crest tissue, found near the level of the coeliac plexus & sympathetic ganglion {{#pmid:16124976|PMID16124976}}. Specifically, this neural crest tissue comes from the trunk neural crest cells (see above figure to determine the approximate location in an embryo) <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> The trunk neural crest coordinates the development of the endocrine system, secretory cells, the peripheral nervous system and, to some degree, skeletal development, as well as innervation of the intestine {{#pmid: 28287247|PMID 28287247}}. The trunk neural cells arise caudally and follow three migratory pathways {{#pmid:20399766|PMID20399766}}.<br /> <br /> - A dorsolateral pathway (between ectoderm and somites)<br /> - A ventrolateral pathway (through the somites)<br /> - A ventromedial pathway (between neural tube and posterior schlerotome){{#pmid:20399766|PMID20399766}}.<br /> <br /> Migration of neural crest cells from the sympathetic ganglion is what leads to the development of the adrenal medulla. In week 8 of development, immature cells called neuroblasts migrate through to the inner portion of the medulla, where they become the adrenal medulla {{#pmid:16392182|PMID16392182}}.<br /> <br /> ===Developmental time course===<br /> ----<br /> <br /> [[File:Adrenal_Medulla_Developmental_Timeline.jpg|right|thumb|500px]]<br /> <br /> The adrenal gland has two distinct sections, the cortex and the medulla, both with different embryonic origins. The cortex accounts for 90% of the adrenal glands and arises from intermediate mesoderm. The medulla only accounts for 10% of the adult adrenal glands, however it has neural crest embryonic origin. The medulla consists of chromaffinoblast cells which are migrant neuroblast cells from the neural crest, therefore the adrenal medulla is a component of the sympathetic nervous system.{{#pmid:21175739|PMID21175739}} Neural crest cells replicate in week 7 and begin to differentiate in week 8, the cells then migrate to the developing adrenal gland in week 9 of development.{{#pmid:25255746|PMID25255746}}{{#pmid:18279781|PMID18279781}} The neural crest cells infiltrate the cortex and the chromaffin cells are scattered islands in the cortex.{{#pmid:23354096|PMID23354096}} Throughout development the cells will become more compact in the centre of the gland, during this period of development the adrenal gland is growing rapidly. The gland is abnormally large until the second trimester and the medulla is much thicker prenatally.{{#pmid:18279781|PMID18279781}}{{#pmid:21175739|PMID21175739}}<br /> <br /> ===Developmental/adult function===<br /> ----<br /> ===Tissue and Organ structure===<br /> <br /> <br /> ====Normal Structure and Function of the Adrenal Medulla====<br /> <br /> The cells of the adrenal medulla are derived from the neural crest as opposed to the mesodermal origins of the cortex. The medulla contains secretory cells called chromaffin cells, due to the agents they produce when oxidised, such as chromate. These cells secrete epinephrine and norepinephrine in response to various substances such as acetylcholine.<br /> <br /> There are three types of cells in the adult adrenal medulla: <br /> 1) Epinephrine cells<br /> <br /> 2) Norepinephrine cells <br /> <br /> 3) Small granule-containing cells (SGCs)<br /> <br /> These cells also produce various other peptides such as substance P and neurotensin. The adrenal medulla also contains presynaptic sympathetic ganglion cells. {{#pmid:1694230|PMID1694230}}<br /> <br /> ====Related Anatomy====<br /> <br /> The tissue and organ structure of the adrenal medulla should be understood with regard to its specialised function within the sympathetic nervous system. <br /> <br /> The medullary region of the adrenal glands is tasked with the endocrine secretions of adrenaline and nor-adrenaline in response to environmental stressors that are signalled for by the sympathetic nervous system. That is, the secretion of fight-or-flight response hormones in order to restrict vasculature to the trunk and increase vascular activity in the peripheral musculature.<br /> <br /> The adrenal glands are supplied by several branches of the great vessels in the abdominal cavity. The secreted catecholamines in the medulla are directly able to pass to the blood stream this way.<br /> <br /> These adrenal glands and their contents are retroperitoneal in the adult and varied in shape, with the left often being semilunar and right being pyramidal. Nervous supply of the adrenal glands is achieved by contributions from the splanchnic nerves of the celiac plexus.<br /> <br /> <br /> ====Role of the Adrenal Medulla====<br /> <br /> Understanding the biochemistry of catecholamines is necessary to see how the adrenal medulla is designed in the stages of embryology and how it is suited for life in the neonate and adult. <br /> <br /> The epinephrine and norepinephrine in the neonate and adult work by primarily changing the osmoregulatory state of vasculature in organs. With the exclusion of their neuromodulatory and neurotransmitter functions, epinephrine and norepinephrine are mainly tasked with the control of sympathetic and parasympathetic supplies. <br /> <br /> Norepinephrine is a constrictor of peripheral vasculature by antagonising the action of surface receptors expressed on the endothelium of blood vessels, specifically Alpha-1 and Alpha-2 receptors, such that vascular resistance increases. <br /> <br /> Epinephrine is both a vasoconstrictor and vasodilator, depending on what receptors it attaches to. As a non-selective adrenergic agonist, it acts on Alpha-1, Alpha-2, Beta-1, Beta-2 and Beta-3 receptors that are found throughout the body's tissues, yielding many different physiological responses.<br /> <br /> <br /> [[File:Dd.jpg|500px|thumb|right|Adult Adrenal Glands in situ]] <br /> ----<br /> <br /> ===Molecular mechanisms/factors/genes===<br /> ----<br /> <br /> ====Genes and Transcription Factors Involved with the Adrenal Medulla's Development====<br /> <br /> Members of the SOX (SRY-Box) gene family have multiple key contributors to Neural Crest in the Adrenal Medulla.<br /> <br /> Mouse models have demonstrated that SOX-10 knock-outs (mice whose DNA has been engineered to not express SOX-10) do not have an adrenal medulla. There has also been suggestion that SOX-8,9 and 10 are all strongly related to the migratory patterning of neural crest cells to the developing adrenal glands.<br /> <br /> The TH gene (for Tyrosine Hydroxylase) encodes the aforementioned enzyme in the adrenal medulla and central nervous system. Tyrosine Hydroxylase is crucial in biochemical pathways and cascades for the synthesis of catecholamines and other CNS neurotransmitters. The conversion from L-Tyrosine to L-DOPA is dependent upon the catalytic action of Tyrosine Hydroxylase. From there, L-DOPA can make Dopamine and eventually Epinephrine and Norepinephrine as well. <br /> <br /> [[File:Catecholamine_Synthesis.jpg|500px|thumb|right|Cascade of Catecholamine Synthesis]]<br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2291442/<br /> https://www.ncbi.nlm.nih.gov/pubmed/19396395<br /> <br /> ===Abnormalities/abnormal development===<br /> ----<br /> ===Animal models===<br /> ----<br /> Animal models are an integral part of research in embryology. In particular due to the moral concerns regarding the use of humans in scientific research. As a result different animals are used as substitutes to simulate the same environments and hope to achieve results that would also be able to represent humans as well. Prenatal adrenal gland development has been described in a number of scientific reports dating from the 1900s to studies in more recent years. These involved a variety of animal models such as ox, sheep, swine and most commonly mice. <br /> <br /> ====Chromaffin cells =(in rat models)====<br /> There has been extensive research conducted into the adrenal chromaffin cells and their embryological developments. As explained above nueral crest cells are pluripotent meaning they are able to differentiate into multiple different cells. The neural crest cells give rise to chromaffin cells of the adrenal medulla.<br /> <br /> To study the formation process of the adrenal medulla in the embryonic period, we visualized chromaffin cells of rat embryos at 13 to 17 days of gestation using anti-tyrosine hydroxylase (TH) antiserum, and created three-dimensional images from serial tissue sections. Between 13 and 15 days of gestation, TH-positive cells (chromaffin cells) migrated from a group of TH-positive cells present dorsal to the adrenal primordium via the medial cranial end of the adrenal primordium into the adrenal primordium. At or after 16 days of gestation, the adrenal capsule was formed except on the ventral aspect of the cranial end of the adrenal gland, from which TH-positive cells penetrated into the adrenal gland.(Pubmed: 15240937) <br /> <br /> Ahonen suggested that some neural crest cells continue migration from the chain ganglia to the lateral sides of aorta, where they form the perirenal ganglia and adrenal medulla, and finally to the ventral side of the aorta to form the preaortic sympathetic tissue. However, that report only showed the several transverse sections of the fetal trunk for the a demonstration of the migration route of neural crest cells. In this study, using three dimensional reconstructed images, we aimed to observe how TH-labeled chromaffin cells penetrate into the adrenal anlage to form the adrenal medulla and whether the migration route of TH - positive cells from the adrenal connects the preaortic sympathetic ganglia <br /> (M.Yamato, R. Yanai, K. Arishima, 2004) <br /> <br /> Prenatal adrenal gland development has been described in numerous published reports covering a wide variety of species, including the ox (Katznelson, 1966; Wrobel and Suss, 1999), sheep (Davies, 1950; Wintour et al., 1975; Upadhyay and Zamboni, 1982; Naaman‐Reperant and Durand, 1997; Grino, 2004), swine (Sokolov et al., 2006) and mouse (Waring, 1935; Ikeda et al., 1994; Sass, 1996; Nyska and Maronpot, 1999; Bland et al., 2003; Val et al., 2007). Adrenal gland development also has been extensively described for humans as well (Kolliker, 1879; Minot, 1892; Zuckerkandl, 1912; Wieman, 1920; Ikeda et al., 1981; Langlois et al., 2002; Hanley and Arit, 2006).<br /> <br /> https://www.sciencedirect.com/science/article/pii/S0925477302004550<br /> http://dev.biologists.org/content/develop/126/13/2935.full.pdf<br /> <br /> ===Current research (labs)===<br /> ----<br /> The findings presented until now have focused on the mechanisms controlling migration along the dorsolateral path. In comparison, our understanding of the mechanisms controlling NCC migration along the ventral path are complicated by the fact that this population comprises multiple precursors that form different derivatives in distinct regions of the embryo. For example, ventrally migrating NCCs either stop within the sclerotome in close association with the neural tube to form neurons and glia of the sensory nervous system (i.e. the dorsal root ganglia [DRG]), while other NCCs continue to migrate further ventrally to form the autonomic nervous system (i.e. sympathetic ganglia and chromaffin cells of the adrenal gland)<br /> <br /> Adrenomedullary chromaffin cells are catecholamine (CA)-producing cells originating from trunk neural crest (NC) via sympathoadrenal progenitors (SAPs). We generated NC and SAPs from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) in vitro via BMP2/FGF2 exposure, ascertained by qPCR and immunoexpression of SOX10, ASCL1, TFAP2α, and PHOX2B, and by fluorescence-activated cell sorting selection for p75NTR and GD2, and confirmed their trunk-like HOX gene expression. We showed that continuing BMP4 and curtailing FGF2 in vitro, augmented with corticosteroid mimetic, induced these cells to upregulate the chromaffin cell-specific marker PNMT and other CA synthesis and storage markers, and we demonstrated noradrenaline and adrenaline by Faglu and high-performance liquid chromatography. We showed these human cells' SAP-like property of migration and differentiation into cells expressing chromaffin cell markers by implanting them into avian embryos in vivo and in chorio-allantoic membrane grafts. These cells have the potential for investigating differentiation of human chromaffin cells and for modeling diseases involving this cell type.<br /> <br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768882/<br /> <br /> ===Glossary===<br /> ----<br /> ===Reference list===</div>

Z5091101 https://embryology.med.unsw.edu.au/embryology/index.php?title=2018_Group_Project_1&diff=356639 2018 Group Project 1 2018-10-10T01:41:00Z

<p>Z5091101: /* Embryonic origins */</p> <hr /> <div>=The Contribution of Neural Crest Cells to the Adrenal Medulla=<br /> ----<br /> {{2018ANAT2341ProjectHeader}}<br /> <br /> <br /> ===Introduction===<br /> [[User:Z5014972|Z5014972]] ([[User talk:Z5014972|talk]]) 12:47, 14 August 2018 (AEST)z5014972 <br /> good review article https://link.springer.com/article/10.1007%2Fs12022-009-9070-6<br /> ----<br /> <br /> <br /> The neural crest of an embryo differentiates and migrates to form various components of the body. One of these tissues is the medulla of the adrenal gland which is involved in the production of adrenalin and noradrenalin. This project will comprehensively outline the history of neural crest research, the embryonic developmental time course, tissue and organ structure, molecular mechanisms, abnormalities, animal models and current research.<br /> <br /> ===History===<br /> ----<br /> '''Describing the neural crest'''<br /> [[File:Wilhelm_His_History_Wilhelm.jpeg|left|230px|thumb|Wilhelm His]]<br /> The "neural crest" is a structure in the embryo and is the junction between the neural and epidermal ectoderm. It is exclusive to vertebrates and forms a range of structures{{#pmid:22230617|PMID22230617}}. The neural crest contributes a large number of cells of varying structure and function that directly or indirectly contribute to the development of tissues and organs within the body {{#pmid:19179766|PMID19179766}}. In 1868, the neural crest cells were first identified in a chick embryo as a collection of cells known as "Zwischenstrang" by Professor Wilhelm His {{#pmid:22820859|PMID22820859}}. Wilhelm His was among the first to provide an explanation for the mechanics governing the developing embryo as well as the physiology and the organs that the differing germinal regions would eventually give rise to. In 1878, the term neural ridge was used to describe this collection of cells but the term neural crest was later coined by Arthur Milnes Marshall in 1879 in a paper he worked on disseminating the knowledge from his research on the development of cranial nerves in chicken embryos. {{#pmid:19179766|PMID19179766}}.<br /> [[File:NC Location.jpg|left|450px|thumb|The neural crest]]<br /> <br /> '''1890s-1950s'''<br /> The neural crest is the point of origin for spinal/cranial ganglia and neurons. This theory received little criticism and was not contested much by other researchers prior to the 1890s. This is owing to the fact that the neural crest is quite closely related to the neural tube and thus this relationship makes sense. This discovery was made by His and Marshall, however, they found this out independently of one another.In the 1890s, Julia Platt, claimed that odontoblasts as well as the cartilages forming the facial and pharyngeal arch skeletons came from the ectoderm. This created much debate and was contested by many{{#pmid:22820859|PMID22820859}}. <br /> <br /> This is because this theory completely contradicted the germ-layer theory, whereby skeletal tissues originate at the mesoderm and not the ectoderm. The controversies this finding created brought about a slowing down of research, as demonstrated by a gap of almost 40 years between the theory that skeletal tissues originating from the neural crest. Today, it is known that the neural crest does indeed play a role in the development of the skeleton in vertebrates, particularly, the cranial neural crest. Although these studies were occurring, the focus was still primarily on researching pigment cells and ganglia of the spine up until the 1950s, when Sven Hörstadius' major work on the neural crest was published, titled "The Neural Crest: Its properties and derivatives in the light of experimental research". This work focused on experimental data tracing the development of the cartilaginous skeleton derived from the neural crest {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1960s - 1970s'''<br /> In the 1960s, the migration patterns of neural crest cells were studied in avian embryos (birds). This was a shift from studying the embryos of amphibians. This was inspired by studies conducted in the 1960s on neural crest cells migrating from the brain and spinal cord, known as trunk and cranial neural crest cells {{#pmid:19179766|PMID19179766}}. The cranial neural crest eventually becomes the bones, cartilage and connective tissues forming the foundation of the face, ears and teeth. The trunk neural crest cells can either become melanocytes or can migrate into sclerotomes which are later contributors to the cartilage of the spine and the dorsal root ganglia {{#pmid:22820859|PMID22820859}}. The cells in the trunk neural crest that migrate vertically become the sympathetic ganglia, the nerves proximal to the aorta and the adrenal medulla <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. In the 1970s many detailed maps signifying the pathways of many of the neural crest cells appeared as well as an understanding that the environment in which the neural crest cells are found plays a major role in their final development as well as the occurrences of abnormalities in the fetus {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1980s - 21st century'''<br /> [[File:Regions_of_NC_Cells.jpg|left|Neural crest regions|thumb]]<br /> From the 1980s-1990s, the causative agent of organ transformation from one to another (homeotic patterning), as well as the Hox genes which regulate the axis of most symmetrical animal embryos were founded and studied. The neural crest, which previously was divided into the cranial and trunk regions, was now further divided into the vagal and sacral neural crest, the cardiac neural crest and the cephalic neural crest {{#pmid:19179766|PMID19179766}}. The vagal & sacral neural crest gives rise to the parasympathetic ganglia found in the gut. Without these ganglia, peristalsis, is not possible <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. The cardiac neural crest contributes to the valves, septa and major blood vessels of the heart, as well as connective tissues and cartilage{{#pmid:19179766|PMID19179766}}. This is important for the structure of the heart as well as its overall function, enabling it to move blood around the body efficiently as well as keep pulmonary and aortic circulation separated <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> <br /> <br /> Today, knowledge of the neural crest cells, their migration patterns, modes of differentiation, derivatives and apoptosis (cell death) are being studied extensively. This is being done on a comparative basis between different organisms, to add further evidence for evolution {{#pmid:19179766|PMID19179766}}. The neural crest is definitely forging a "crest" between the fields of developmental and evolutionary biology, as it is a structure '''shared exclusively by all vertebrates'''. Invertebrates do not derive their specialised cells from the neural crest as they do not have one, rather, they derive these from the endomesoderm {{#pmid:22230617|PMID22230617}}.<br /> <br /> '''Future directions'''<br /> <br /> Since its discovery by His, the neural crest field has made great progress, from studies performed on the structure, to analysis of the molecules and whether certain aspects of the neural crest are specific to a single species of organism, or to all vertebrates collectively. Future work on the cranial neural crest needs to be done as well as identifying and categorising the networks responsible for the proliferation and death of cells, as well as how the cells move and migrate, as well as the gene regulatory networks (GRNs) that regulate the synthesis of proteins. Advances in technology will undeniable lead us to more answers on the subject {{#pmid:22230617|PMID22230617}}.<br /> <br /> ===Embryonic origins===<br /> ----<br /> https://www.ncbi.nlm.nih.gov/books/NBK10065/<br /> <br /> The adrenal gland is made up of the adrenal cortex and adrenal medulla, which both have different embryonic origins. The adrenal medulla arises from the neural crest tissue, found near the level of the coeliac plexus & sympathetic ganglion {{#pmid:16124976|PMID16124976}}. Specifically, this neural crest tissue comes from the trunk neural crest cells (see above figure to determine the approximate location in an embryo) <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> The trunk neural crest coordinates the development of the endocrine system, secretory cells, the peripheral nervous system and, to some degree, skeletal development, as well as innervation of the intestine {{#pmid: 28287247|PMID 28287247}}. The trunk neural cells arise caudally and follow three migratory pathways {{#pmid:20399766|PMID20399766}}.<br /> <br /> - A dorsolateral pathway (between ectoderm and somites)<br /> - A ventrolateral pathway (through the somites)<br /> - A ventromedial pathway (between neural tube and posterior schlerotome){{#pmid:20399766|PMID20399766}}.<br /> <br /> ===Developmental time course===<br /> ----<br /> <br /> [[File:Adrenal_Medulla_Developmental_Timeline.jpg|right|thumb|500px]]<br /> <br /> The adrenal gland has two distinct sections, the cortex and the medulla, both with different embryonic origins. The cortex accounts for 90% of the adrenal glands and arises from intermediate mesoderm. The medulla only accounts for 10% of the adult adrenal glands, however it has neural crest embryonic origin. The medulla consists of chromaffinoblast cells which are migrant neuroblast cells from the neural crest, therefore the adrenal medulla is a component of the sympathetic nervous system.{{#pmid:21175739|PMID21175739}} Neural crest cells replicate in week 7 and begin to differentiate in week 8, the cells then migrate to the developing adrenal gland in week 9 of development.{{#pmid:25255746|PMID25255746}}{{#pmid:18279781|PMID18279781}} The neural crest cells infiltrate the cortex and the chromaffin cells are scattered islands in the cortex.{{#pmid:23354096|PMID23354096}} Throughout development the cells will become more compact in the centre of the gland, during this period of development the adrenal gland is growing rapidly. The gland is abnormally large until the second trimester and the medulla is much thicker prenatally.{{#pmid:18279781|PMID18279781}}{{#pmid:21175739|PMID21175739}}<br /> <br /> ===Developmental/adult function===<br /> ----<br /> ===Tissue and Organ structure===<br /> <br /> <br /> ====Normal Structure and Function of the Adrenal Medulla====<br /> <br /> The cells of the adrenal medulla are derived from the neural crest as opposed to the mesodermal origins of the cortex. The medulla contains secretory cells called chromaffin cells, due to the agents they produce when oxidised, such as chromate. These cells secrete epinephrine and norepinephrine in response to various substances such as acetylcholine.<br /> <br /> There are three types of cells in the adult adrenal medulla: <br /> 1) Epinephrine cells<br /> <br /> 2) Norepinephrine cells <br /> <br /> 3) Small granule-containing cells (SGCs)<br /> <br /> These cells also produce various other peptides such as substance P and neurotensin. The adrenal medulla also contains presynaptic sympathetic ganglion cells. {{#pmid:1694230|PMID1694230}}<br /> <br /> ====Related Anatomy====<br /> <br /> The tissue and organ structure of the adrenal medulla should be understood with regard to its specialised function within the sympathetic nervous system. <br /> <br /> The medullary region of the adrenal glands is tasked with the endocrine secretions of adrenaline and nor-adrenaline in response to environmental stressors that are signalled for by the sympathetic nervous system. That is, the secretion of fight-or-flight response hormones in order to restrict vasculature to the trunk and increase vascular activity in the peripheral musculature.<br /> <br /> The adrenal glands are supplied by several branches of the great vessels in the abdominal cavity. The secreted catecholamines in the medulla are directly able to pass to the blood stream this way.<br /> <br /> These adrenal glands and their contents are retroperitoneal in the adult and varied in shape, with the left often being semilunar and right being pyramidal. Nervous supply of the adrenal glands is achieved by contributions from the splanchnic nerves of the celiac plexus.<br /> <br /> <br /> ====Role of the Adrenal Medulla====<br /> <br /> Understanding the biochemistry of catecholamines is necessary to see how the adrenal medulla is designed in the stages of embryology and how it is suited for life in the neonate and adult. <br /> <br /> The epinephrine and norepinephrine in the neonate and adult work by primarily changing the osmoregulatory state of vasculature in organs. With the exclusion of their neuromodulatory and neurotransmitter functions, epinephrine and norepinephrine are mainly tasked with the control of sympathetic and parasympathetic supplies. <br /> <br /> Norepinephrine is a constrictor of peripheral vasculature by antagonising the action of surface receptors expressed on the endothelium of blood vessels, specifically Alpha-1 and Alpha-2 receptors, such that vascular resistance increases. <br /> <br /> Epinephrine is both a vasoconstrictor and vasodilator, depending on what receptors it attaches to. As a non-selective adrenergic agonist, it acts on Alpha-1, Alpha-2, Beta-1, Beta-2 and Beta-3 receptors that are found throughout the body's tissues, yielding many different physiological responses.<br /> <br /> <br /> [[File:Dd.jpg|500px|thumb|right|Adult Adrenal Glands in situ]] <br /> ----<br /> <br /> ===Molecular mechanisms/factors/genes===<br /> ----<br /> <br /> ====Genes and Transcription Factors Involved with the Adrenal Medulla's Development====<br /> <br /> Members of the SOX (SRY-Box) gene family have multiple key contributors to Neural Crest in the Adrenal Medulla.<br /> <br /> Mouse models have demonstrated that SOX-10 knock-outs (mice whose DNA has been engineered to not express SOX-10) do not have an adrenal medulla. There has also been suggestion that SOX-8,9 and 10 are all strongly related to the migratory patterning of neural crest cells to the developing adrenal glands.<br /> <br /> The TH gene (for Tyrosine Hydroxylase) encodes the aforementioned enzyme in the adrenal medulla and central nervous system. Tyrosine Hydroxylase is crucial in biochemical pathways and cascades for the synthesis of catecholamines and other CNS neurotransmitters. The conversion from L-Tyrosine to L-DOPA is dependent upon the catalytic action of Tyrosine Hydroxylase. From there, L-DOPA can make Dopamine and eventually Epinephrine and Norepinephrine as well. <br /> <br /> [[File:Catecholamine_Synthesis.jpg|500px|thumb|right|Cascade of Catecholamine Synthesis]]<br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2291442/<br /> https://www.ncbi.nlm.nih.gov/pubmed/19396395<br /> <br /> ===Abnormalities/abnormal development===<br /> ----<br /> ===Animal models===<br /> ----<br /> Animal models are an integral part of research in embryology. In particular due to the moral concerns regarding the use of humans in scientific research. As a result different animals are used as substitutes to simulate the same environments and hope to achieve results that would also be able to represent humans as well. Prenatal adrenal gland development has been described in a number of scientific reports dating from the 1900s to studies in more recent years. These involved a variety of animal models such as ox, sheep, swine and most commonly mice. <br /> <br /> ====Chromaffin cells =(in rat models)====<br /> There has been extensive research conducted into the adrenal chromaffin cells and their embryological developments. As explained above nueral crest cells are pluripotent meaning they are able to differentiate into multiple different cells. The neural crest cells give rise to chromaffin cells of the adrenal medulla.<br /> <br /> To study the formation process of the adrenal medulla in the embryonic period, we visualized chromaffin cells of rat embryos at 13 to 17 days of gestation using anti-tyrosine hydroxylase (TH) antiserum, and created three-dimensional images from serial tissue sections. Between 13 and 15 days of gestation, TH-positive cells (chromaffin cells) migrated from a group of TH-positive cells present dorsal to the adrenal primordium via the medial cranial end of the adrenal primordium into the adrenal primordium. At or after 16 days of gestation, the adrenal capsule was formed except on the ventral aspect of the cranial end of the adrenal gland, from which TH-positive cells penetrated into the adrenal gland.(Pubmed: 15240937) <br /> <br /> Ahonen suggested that some neural crest cells continue migration from the chain ganglia to the lateral sides of aorta, where they form the perirenal ganglia and adrenal medulla, and finally to the ventral side of the aorta to form the preaortic sympathetic tissue. However, that report only showed the several transverse sections of the fetal trunk for the a demonstration of the migration route of neural crest cells. In this study, using three dimensional reconstructed images, we aimed to observe how TH-labeled chromaffin cells penetrate into the adrenal anlage to form the adrenal medulla and whether the migration route of TH - positive cells from the adrenal connects the preaortic sympathetic ganglia <br /> (M.Yamato, R. Yanai, K. Arishima, 2004) <br /> <br /> Prenatal adrenal gland development has been described in numerous published reports covering a wide variety of species, including the ox (Katznelson, 1966; Wrobel and Suss, 1999), sheep (Davies, 1950; Wintour et al., 1975; Upadhyay and Zamboni, 1982; Naaman‐Reperant and Durand, 1997; Grino, 2004), swine (Sokolov et al., 2006) and mouse (Waring, 1935; Ikeda et al., 1994; Sass, 1996; Nyska and Maronpot, 1999; Bland et al., 2003; Val et al., 2007). Adrenal gland development also has been extensively described for humans as well (Kolliker, 1879; Minot, 1892; Zuckerkandl, 1912; Wieman, 1920; Ikeda et al., 1981; Langlois et al., 2002; Hanley and Arit, 2006).<br /> <br /> https://www.sciencedirect.com/science/article/pii/S0925477302004550<br /> http://dev.biologists.org/content/develop/126/13/2935.full.pdf<br /> <br /> ===Current research (labs)===<br /> ----<br /> The findings presented until now have focused on the mechanisms controlling migration along the dorsolateral path. In comparison, our understanding of the mechanisms controlling NCC migration along the ventral path are complicated by the fact that this population comprises multiple precursors that form different derivatives in distinct regions of the embryo. For example, ventrally migrating NCCs either stop within the sclerotome in close association with the neural tube to form neurons and glia of the sensory nervous system (i.e. the dorsal root ganglia [DRG]), while other NCCs continue to migrate further ventrally to form the autonomic nervous system (i.e. sympathetic ganglia and chromaffin cells of the adrenal gland)<br /> <br /> Adrenomedullary chromaffin cells are catecholamine (CA)-producing cells originating from trunk neural crest (NC) via sympathoadrenal progenitors (SAPs). We generated NC and SAPs from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) in vitro via BMP2/FGF2 exposure, ascertained by qPCR and immunoexpression of SOX10, ASCL1, TFAP2α, and PHOX2B, and by fluorescence-activated cell sorting selection for p75NTR and GD2, and confirmed their trunk-like HOX gene expression. We showed that continuing BMP4 and curtailing FGF2 in vitro, augmented with corticosteroid mimetic, induced these cells to upregulate the chromaffin cell-specific marker PNMT and other CA synthesis and storage markers, and we demonstrated noradrenaline and adrenaline by Faglu and high-performance liquid chromatography. We showed these human cells' SAP-like property of migration and differentiation into cells expressing chromaffin cell markers by implanting them into avian embryos in vivo and in chorio-allantoic membrane grafts. These cells have the potential for investigating differentiation of human chromaffin cells and for modeling diseases involving this cell type.<br /> <br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768882/<br /> <br /> ===Glossary===<br /> ----<br /> ===Reference list===</div>

Z5091101 https://embryology.med.unsw.edu.au/embryology/index.php?title=2018_Group_Project_1&diff=356599 2018 Group Project 1 2018-10-10T00:58:05Z

<p>Z5091101: /* Embryonic origins */</p> <hr /> <div>=The Contribution of Neural Crest Cells to the Adrenal Medulla=<br /> ----<br /> {{2018ANAT2341ProjectHeader}}<br /> <br /> <br /> ===Introduction===<br /> [[User:Z5014972|Z5014972]] ([[User talk:Z5014972|talk]]) 12:47, 14 August 2018 (AEST)z5014972 <br /> good review article https://link.springer.com/article/10.1007%2Fs12022-009-9070-6<br /> ----<br /> <br /> <br /> The neural crest of an embryo differentiates and migrates to form various components of the body. One of these tissues is the medulla of the adrenal gland which is involved in the production of adrenalin and noradrenalin. This project will comprehensively outline the history of neural crest research, the embryonic developmental time course, tissue and organ structure, molecular mechanisms, abnormalities, animal models and current research.<br /> <br /> ===History===<br /> ----<br /> '''Describing the neural crest'''<br /> [[File:Wilhelm_His_History_Wilhelm.jpeg|left|230px|thumb|Wilhelm His]]<br /> The "neural crest" is a structure in the embryo and is the junction between the neural and epidermal ectoderm. It is exclusive to vertebrates and forms a range of structures{{#pmid:22230617|PMID22230617}}. The neural crest contributes a large number of cells of varying structure and function that directly or indirectly contribute to the development of tissues and organs within the body {{#pmid:19179766|PMID19179766}}. In 1868, the neural crest cells were first identified in a chick embryo as a collection of cells known as "Zwischenstrang" by Professor Wilhelm His {{#pmid:22820859|PMID22820859}}. Wilhelm His was among the first to provide an explanation for the mechanics governing the developing embryo as well as the physiology and the organs that the differing germinal regions would eventually give rise to. In 1878, the term neural ridge was used to describe this collection of cells but the term neural crest was later coined by Arthur Milnes Marshall in 1879 in a paper he worked on disseminating the knowledge from his research on the development of cranial nerves in chicken embryos. {{#pmid:19179766|PMID19179766}}.<br /> [[File:NC Location.jpg|left|450px|thumb|The neural crest]]<br /> <br /> '''1890s-1950s'''<br /> The neural crest is the point of origin for spinal/cranial ganglia and neurons. This theory received little criticism and was not contested much by other researchers prior to the 1890s. This is owing to the fact that the neural crest is quite closely related to the neural tube and thus this relationship makes sense. This discovery was made by His and Marshall, however, they found this out independently of one another.In the 1890s, Julia Platt, claimed that odontoblasts as well as the cartilages forming the facial and pharyngeal arch skeletons came from the ectoderm. This created much debate and was contested by many{{#pmid:22820859|PMID22820859}}. <br /> <br /> This is because this theory completely contradicted the germ-layer theory, whereby skeletal tissues originate at the mesoderm and not the ectoderm. The controversies this finding created brought about a slowing down of research, as demonstrated by a gap of almost 40 years between the theory that skeletal tissues originating from the neural crest. Today, it is known that the neural crest does indeed play a role in the development of the skeleton in vertebrates, particularly, the cranial neural crest. Although these studies were occurring, the focus was still primarily on researching pigment cells and ganglia of the spine up until the 1950s, when Sven Hörstadius' major work on the neural crest was published, titled "The Neural Crest: Its properties and derivatives in the light of experimental research". This work focused on experimental data tracing the development of the cartilaginous skeleton derived from the neural crest {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1960s - 1970s'''<br /> In the 1960s, the migration patterns of neural crest cells were studied in avian embryos (birds). This was a shift from studying the embryos of amphibians. This was inspired by studies conducted in the 1960s on neural crest cells migrating from the brain and spinal cord, known as trunk and cranial neural crest cells {{#pmid:19179766|PMID19179766}}. The cranial neural crest eventually becomes the bones, cartilage and connective tissues forming the foundation of the face, ears and teeth. The trunk neural crest cells can either become melanocytes or can migrate into sclerotomes which are later contributors to the cartilage of the spine and the dorsal root ganglia {{#pmid:22820859|PMID22820859}}. The cells in the trunk neural crest that migrate vertically become the sympathetic ganglia, the nerves proximal to the aorta and the adrenal medulla <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. In the 1970s many detailed maps signifying the pathways of many of the neural crest cells appeared as well as an understanding that the environment in which the neural crest cells are found plays a major role in their final development as well as the occurrences of abnormalities in the fetus {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1980s - 21st century'''<br /> [[File:Regions_of_NC_Cells.jpg|left|Neural crest regions|thumb]]<br /> From the 1980s-1990s, the causative agent of organ transformation from one to another (homeotic patterning), as well as the Hox genes which regulate the axis of most symmetrical animal embryos were founded and studied. The neural crest, which previously was divided into the cranial and trunk regions, was now further divided into the vagal and sacral neural crest, the cardiac neural crest and the cephalic neural crest {{#pmid:19179766|PMID19179766}}. The vagal & sacral neural crest gives rise to the parasympathetic ganglia found in the gut. Without these ganglia, peristalsis, is not possible <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. The cardiac neural crest contributes to the valves, septa and major blood vessels of the heart, as well as connective tissues and cartilage{{#pmid:19179766|PMID19179766}}. This is important for the structure of the heart as well as its overall function, enabling it to move blood around the body efficiently as well as keep pulmonary and aortic circulation separated <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> <br /> <br /> Today, knowledge of the neural crest cells, their migration patterns, modes of differentiation, derivatives and apoptosis (cell death) are being studied extensively. This is being done on a comparative basis between different organisms, to add further evidence for evolution {{#pmid:19179766|PMID19179766}}. The neural crest is definitely forging a "crest" between the fields of developmental and evolutionary biology, as it is a structure '''shared exclusively by all vertebrates'''. Invertebrates do not derive their specialised cells from the neural crest as they do not have one, rather, they derive these from the endomesoderm {{#pmid:22230617|PMID22230617}}.<br /> <br /> '''Future directions'''<br /> <br /> Since its discovery by His, the neural crest field has made great progress, from studies performed on the structure, to analysis of the molecules and whether certain aspects of the neural crest are specific to a single species of organism, or to all vertebrates collectively. Future work on the cranial neural crest needs to be done as well as identifying and categorising the networks responsible for the proliferation and death of cells, as well as how the cells move and migrate, as well as the gene regulatory networks (GRNs) that regulate the synthesis of proteins. Advances in technology will undeniable lead us to more answers on the subject {{#pmid:22230617|PMID22230617}}.<br /> <br /> ===Embryonic origins===<br /> ----<br /> https://www.ncbi.nlm.nih.gov/books/NBK10065/<br /> <br /> The adrenal gland is made up of the adrenal cortex and adrenal medulla, which both have different embryonic origins. The adrenal medulla arises from the neural crest tissue, found near the level of the coeliac plexus & sympathetic ganglion {{#pmid:16124976|PMID16124976}}. Specifically, this neural crest tissue comes from the trunk neural crest cells (see above figure to determine the approximate location in an embryo) <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> The trunk neural crest coordinates the development of the endocrine system, secretory cells, the peripheral nervous system and, to some degree, skeletal development, as well as innervation of the intestine {{#pmid: 28287247|PMID 28287247}}. The trunk neural cells arise caudally and follow three migratory pathways {{#pmid:20399766|PMID20399766}}.<br /> <br /> - A dorsolateral pathway (between ectoderm and somites)<br /> - A ventrolateral pathway (through the somites)<br /> - A ventromedial pathway (between neural tube and posterior schlerotome){{#pmid:20399766|PMID20399766}}.<br /> <br /> Somites are collections of paraxial mesoderm that are located from the head to the tail of the embryo, forming skeletal structures, cartilages and tendons of the back <ref>name="Larsen">{{cite book|last1=Larsen|first1=William J.|title=Human embryology|date=2001|publisher=Churchill Livingstone|location=Philadelphia, Pa.|isbn=0-443-06583-7|pages=53–86|edition=3.}}</ref>.<br /> <br /> ===Developmental time course===<br /> ----<br /> <br /> [[File:Adrenal_Medulla_Developmental_Timeline.jpg|right|thumb|500px]]<br /> <br /> The adrenal gland has two distinct sections, the cortex and the medulla, both with different embryonic origins. The cortex accounts for 90% of the adrenal glands and arises from intermediate mesoderm. The medulla only accounts for 10% of the adult adrenal glands, however it has neural crest embryonic origin. The medulla consists of chromaffinoblast cells which are migrant neuroblast cells from the neural crest, therefore the adrenal medulla is a component of the sympathetic nervous system.{{#pmid:21175739|PMID21175739}} Neural crest cells replicate in week 7 and begin to differentiate in week 8, the cells then migrate to the developing adrenal gland in week 9 of development.{{#pmid:25255746|PMID25255746}}{{#pmid:18279781|PMID18279781}} The neural crest cells infiltrate the cortex and the chromaffin cells are scattered islands in the cortex.{{#pmid:23354096|PMID23354096}} Throughout development the cells will become more compact in the centre of the gland, during this period of development the adrenal gland is growing rapidly. The gland is abnormally large until the second trimester and the medulla is much thicker prenatally.{{#pmid:18279781|PMID18279781}}{{#pmid:21175739|PMID21175739}}<br /> <br /> ===Developmental/adult function===<br /> ----<br /> ===Tissue and Organ structure===<br /> <br /> <br /> ====Normal Structure and Function of the Adrenal Medulla====<br /> <br /> The cells of the adrenal medulla are derived from the neural crest as opposed to the mesodermal origins of the cortex. The medulla contains secretory cells called chromaffin cells, due to the agents they produce when oxidised, such as chromate. These cells secrete epinephrine and norepinephrine in response to various substances such as acetylcholine.<br /> <br /> There are three types of cells in the adult adrenal medulla: <br /> 1) Epinephrine cells<br /> <br /> 2) Norepinephrine cells <br /> <br /> 3) Small granule-containing cells (SGCs)<br /> <br /> These cells also produce various other peptides such as substance P and neurotensin. The adrenal medulla also contains presynaptic sympathetic ganglion cells. {{#pmid:1694230|PMID1694230}}<br /> <br /> ====Related Anatomy====<br /> <br /> The tissue and organ structure of the adrenal medulla should be understood with regard to its specialised function within the sympathetic nervous system. <br /> <br /> The medullary region of the adrenal glands is tasked with the endocrine secretions of adrenaline and nor-adrenaline in response to environmental stressors that are signalled for by the sympathetic nervous system. That is, the secretion of fight-or-flight response hormones in order to restrict vasculature to the trunk and increase vascular activity in the peripheral musculature.<br /> <br /> The adrenal glands are supplied by several branches of the great vessels in the abdominal cavity. The secreted catecholamines in the medulla are directly able to pass to the blood stream this way.<br /> <br /> These adrenal glands and their contents are retroperitoneal in the adult and varied in shape, with the left often being semilunar and right being pyramidal. Nervous supply of the adrenal glands is achieved by contributions from the splanchnic nerves of the celiac plexus.<br /> <br /> <br /> ====Role of the Adrenal Medulla====<br /> <br /> Understanding the biochemistry of catecholamines is necessary to see how the adrenal medulla is designed in the stages of embryology and how it is suited for life in the neonate and adult. <br /> <br /> The epinephrine and norepinephrine in the neonate and adult work by primarily changing the osmoregulatory state of vasculature in organs. With the exclusion of their neuromodulatory and neurotransmitter functions, epinephrine and norepinephrine are mainly tasked with the control of sympathetic and parasympathetic supplies. <br /> <br /> Norepinephrine is a constrictor of peripheral vasculature by antagonising the action of surface receptors expressed on the endothelium of blood vessels, specifically Alpha-1 and Alpha-2 receptors, such that vascular resistance increases. <br /> <br /> Epinephrine is both a vasoconstrictor and vasodilator, depending on what receptors it attaches to. As a non-selective adrenergic agonist, it acts on Alpha-1, Alpha-2, Beta-1, Beta-2 and Beta-3 receptors that are found throughout the body's tissues, yielding many different physiological responses.<br /> <br /> <br /> [[File:Dd.jpg|500px|thumb|right|Adult Adrenal Glands in situ]] <br /> ----<br /> <br /> ===Molecular mechanisms/factors/genes===<br /> ----<br /> <br /> ====Genes and Transcription Factors Involved with the Adrenal Medulla's Development====<br /> <br /> Members of the SOX (SRY-Box) gene family have multiple key contributors to Neural Crest in the Adrenal Medulla.<br /> <br /> Mouse models have demonstrated that SOX-10 knock-outs (mice whose DNA has been engineered to not express SOX-10) do not have an adrenal medulla. There has also been suggestion that SOX-8,9 and 10 are all strongly related to the migratory patterning of neural crest cells to the developing adrenal glands.<br /> <br /> The TH gene (for Tyrosine Hydroxylase) encodes the aforementioned enzyme in the adrenal medulla and central nervous system. Tyrosine Hydroxylase is crucial in biochemical pathways and cascades for the synthesis of catecholamines and other CNS neurotransmitters. The conversion from L-Tyrosine to L-DOPA is dependent upon the catalytic action of Tyrosine Hydroxylase. From there, L-DOPA can make Dopamine and eventually Epinephrine and Norepinephrine as well. <br /> <br /> [[File:Catecholamine_Synthesis.jpg|500px|thumb|right|Cascade of Catecholamine Synthesis]]<br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2291442/<br /> https://www.ncbi.nlm.nih.gov/pubmed/19396395<br /> <br /> ===Abnormalities/abnormal development===<br /> ----<br /> ===Animal models===<br /> ----<br /> Animal models are an integral part of research in embryology. In particular due to the moral concerns regarding the use of humans in scientific research. As a result different animals are used as substitutes to simulate the same environments and hope to achieve results that would also be able to represent humans as well. Prenatal adrenal gland development has been described in a number of scientific reports dating from the 1900s to studies in more recent years. These involved a variety of animal models such as ox, sheep, swine and most commonly mice. <br /> <br /> ====Chromaffin cells =(in rat models)====<br /> There has been extensive research conducted into the adrenal chromaffin cells and their embryological developments. As explained above nueral crest cells are pluripotent meaning they are able to differentiate into multiple different cells. The neural crest cells give rise to chromaffin cells of the adrenal medulla.<br /> <br /> To study the formation process of the adrenal medulla in the embryonic period, we visualized chromaffin cells of rat embryos at 13 to 17 days of gestation using anti-tyrosine hydroxylase (TH) antiserum, and created three-dimensional images from serial tissue sections. Between 13 and 15 days of gestation, TH-positive cells (chromaffin cells) migrated from a group of TH-positive cells present dorsal to the adrenal primordium via the medial cranial end of the adrenal primordium into the adrenal primordium. At or after 16 days of gestation, the adrenal capsule was formed except on the ventral aspect of the cranial end of the adrenal gland, from which TH-positive cells penetrated into the adrenal gland.(Pubmed: 15240937) <br /> <br /> Ahonen suggested that some neural crest cells continue migration from the chain ganglia to the lateral sides of aorta, where they form the perirenal ganglia and adrenal medulla, and finally to the ventral side of the aorta to form the preaortic sympathetic tissue. However, that report only showed the several transverse sections of the fetal trunk for the a demonstration of the migration route of neural crest cells. In this study, using three dimensional reconstructed images, we aimed to observe how TH-labeled chromaffin cells penetrate into the adrenal anlage to form the adrenal medulla and whether the migration route of TH - positive cells from the adrenal connects the preaortic sympathetic ganglia <br /> (M.Yamato, R. Yanai, K. Arishima, 2004) <br /> <br /> Prenatal adrenal gland development has been described in numerous published reports covering a wide variety of species, including the ox (Katznelson, 1966; Wrobel and Suss, 1999), sheep (Davies, 1950; Wintour et al., 1975; Upadhyay and Zamboni, 1982; Naaman‐Reperant and Durand, 1997; Grino, 2004), swine (Sokolov et al., 2006) and mouse (Waring, 1935; Ikeda et al., 1994; Sass, 1996; Nyska and Maronpot, 1999; Bland et al., 2003; Val et al., 2007). Adrenal gland development also has been extensively described for humans as well (Kolliker, 1879; Minot, 1892; Zuckerkandl, 1912; Wieman, 1920; Ikeda et al., 1981; Langlois et al., 2002; Hanley and Arit, 2006).<br /> <br /> https://www.sciencedirect.com/science/article/pii/S0925477302004550<br /> http://dev.biologists.org/content/develop/126/13/2935.full.pdf<br /> <br /> ===Current research (labs)===<br /> ----<br /> The findings presented until now have focused on the mechanisms controlling migration along the dorsolateral path. In comparison, our understanding of the mechanisms controlling NCC migration along the ventral path are complicated by the fact that this population comprises multiple precursors that form different derivatives in distinct regions of the embryo. For example, ventrally migrating NCCs either stop within the sclerotome in close association with the neural tube to form neurons and glia of the sensory nervous system (i.e. the dorsal root ganglia [DRG]), while other NCCs continue to migrate further ventrally to form the autonomic nervous system (i.e. sympathetic ganglia and chromaffin cells of the adrenal gland)<br /> <br /> Adrenomedullary chromaffin cells are catecholamine (CA)-producing cells originating from trunk neural crest (NC) via sympathoadrenal progenitors (SAPs). We generated NC and SAPs from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) in vitro via BMP2/FGF2 exposure, ascertained by qPCR and immunoexpression of SOX10, ASCL1, TFAP2α, and PHOX2B, and by fluorescence-activated cell sorting selection for p75NTR and GD2, and confirmed their trunk-like HOX gene expression. We showed that continuing BMP4 and curtailing FGF2 in vitro, augmented with corticosteroid mimetic, induced these cells to upregulate the chromaffin cell-specific marker PNMT and other CA synthesis and storage markers, and we demonstrated noradrenaline and adrenaline by Faglu and high-performance liquid chromatography. We showed these human cells' SAP-like property of migration and differentiation into cells expressing chromaffin cell markers by implanting them into avian embryos in vivo and in chorio-allantoic membrane grafts. These cells have the potential for investigating differentiation of human chromaffin cells and for modeling diseases involving this cell type.<br /> <br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768882/<br /> <br /> ===Glossary===<br /> ----<br /> ===Reference list===</div>

Z5091101 https://embryology.med.unsw.edu.au/embryology/index.php?title=2018_Group_Project_1&diff=356543 2018 Group Project 1 2018-10-09T07:58:59Z

<p>Z5091101: /* Embryonic origins */</p> <hr /> <div>=The Contribution of Neural Crest Cells to the Adrenal Medulla=<br /> ----<br /> {{2018ANAT2341ProjectHeader}}<br /> <br /> <br /> ===Introduction===<br /> [[User:Z5014972|Z5014972]] ([[User talk:Z5014972|talk]]) 12:47, 14 August 2018 (AEST)z5014972 <br /> good review article https://link.springer.com/article/10.1007%2Fs12022-009-9070-6<br /> ----<br /> <br /> <br /> The neural crest of an embryo differentiates and migrates to form various components of the body. One of these tissues is the medulla of the adrenal gland which is involved in the production of adrenalin and noradrenalin. This project will comprehensively outline the history of neural crest research, the embryonic developmental time course, tissue and organ structure, molecular mechanisms, abnormalities, animal models and current research.<br /> <br /> ===History===<br /> ----<br /> '''Describing the neural crest'''<br /> [[File:Wilhelm_His_History_Wilhelm.jpeg|left|230px|thumb|Wilhelm His]]<br /> The "neural crest" is a structure in the embryo and is the junction between the neural and epidermal ectoderm. It is exclusive to vertebrates and forms a range of structures{{#pmid:22230617|PMID22230617}}. The neural crest contributes a large number of cells of varying structure and function that directly or indirectly contribute to the development of tissues and organs within the body {{#pmid:19179766|PMID19179766}}. In 1868, the neural crest cells were first identified in a chick embryo as a collection of cells known as "Zwischenstrang" by Professor Wilhelm His {{#pmid:22820859|PMID22820859}}. Wilhelm His was among the first to provide an explanation for the mechanics governing the developing embryo as well as the physiology and the organs that the differing germinal regions would eventually give rise to. In 1878, the term neural ridge was used to describe this collection of cells but the term neural crest was later coined by Arthur Milnes Marshall in 1879 in a paper he worked on disseminating the knowledge from his research on the development of cranial nerves in chicken embryos. {{#pmid:19179766|PMID19179766}}.<br /> [[File:NC Location.jpg|left|450px|thumb|The neural crest]]<br /> <br /> '''1890s-1950s'''<br /> The neural crest is the point of origin for spinal/cranial ganglia and neurons. This theory received little criticism and was not contested much by other researchers prior to the 1890s. This is owing to the fact that the neural crest is quite closely related to the neural tube and thus this relationship makes sense. This discovery was made by His and Marshall, however, they found this out independently of one another.In the 1890s, Julia Platt, claimed that odontoblasts as well as the cartilages forming the facial and pharyngeal arch skeletons came from the ectoderm. This created much debate and was contested by many{{#pmid:22820859|PMID22820859}}. <br /> <br /> This is because this theory completely contradicted the germ-layer theory, whereby skeletal tissues originate at the mesoderm and not the ectoderm. The controversies this finding created brought about a slowing down of research, as demonstrated by a gap of almost 40 years between the theory that skeletal tissues originating from the neural crest. Today, it is known that the neural crest does indeed play a role in the development of the skeleton in vertebrates, particularly, the cranial neural crest. Although these studies were occurring, the focus was still primarily on researching pigment cells and ganglia of the spine up until the 1950s, when Sven Hörstadius' major work on the neural crest was published, titled "The Neural Crest: Its properties and derivatives in the light of experimental research". This work focused on experimental data tracing the development of the cartilaginous skeleton derived from the neural crest {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1960s - 1970s'''<br /> In the 1960s, the migration patterns of neural crest cells were studied in avian embryos (birds). This was a shift from studying the embryos of amphibians. This was inspired by studies conducted in the 1960s on neural crest cells migrating from the brain and spinal cord, known as trunk and cranial neural crest cells {{#pmid:19179766|PMID19179766}}. The cranial neural crest eventually becomes the bones, cartilage and connective tissues forming the foundation of the face, ears and teeth. The trunk neural crest cells can either become melanocytes or can migrate into sclerotomes which are later contributors to the cartilage of the spine and the dorsal root ganglia {{#pmid:22820859|PMID22820859}}. The cells in the trunk neural crest that migrate vertically become the sympathetic ganglia, the nerves proximal to the aorta and the adrenal medulla <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. In the 1970s many detailed maps signifying the pathways of many of the neural crest cells appeared as well as an understanding that the environment in which the neural crest cells are found plays a major role in their final development as well as the occurrences of abnormalities in the fetus {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1980s - 21st century'''<br /> [[File:Regions_of_NC_Cells.jpg|left|Neural crest regions|thumb]]<br /> From the 1980s-1990s, the causative agent of organ transformation from one to another (homeotic patterning), as well as the Hox genes which regulate the axis of most symmetrical animal embryos were founded and studied. The neural crest, which previously was divided into the cranial and trunk regions, was now further divided into the vagal and sacral neural crest, the cardiac neural crest and the cephalic neural crest {{#pmid:19179766|PMID19179766}}. The vagal & sacral neural crest gives rise to the parasympathetic ganglia found in the gut. Without these ganglia, peristalsis, is not possible <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. The cardiac neural crest contributes to the valves, septa and major blood vessels of the heart, as well as connective tissues and cartilage{{#pmid:19179766|PMID19179766}}. This is important for the structure of the heart as well as its overall function, enabling it to move blood around the body efficiently as well as keep pulmonary and aortic circulation separated <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> <br /> <br /> Today, knowledge of the neural crest cells, their migration patterns, modes of differentiation, derivatives and apoptosis (cell death) are being studied extensively. This is being done on a comparative basis between different organisms, to add further evidence for evolution {{#pmid:19179766|PMID19179766}}. The neural crest is definitely forging a "crest" between the fields of developmental and evolutionary biology, as it is a structure '''shared exclusively by all vertebrates'''. Invertebrates do not derive their specialised cells from the neural crest as they do not have one, rather, they derive these from the endomesoderm {{#pmid:22230617|PMID22230617}}.<br /> <br /> '''Future directions'''<br /> <br /> Since its discovery by His, the neural crest field has made great progress, from studies performed on the structure, to analysis of the molecules and whether certain aspects of the neural crest are specific to a single species of organism, or to all vertebrates collectively. Future work on the cranial neural crest needs to be done as well as identifying and categorising the networks responsible for the proliferation and death of cells, as well as how the cells move and migrate, as well as the gene regulatory networks (GRNs) that regulate the synthesis of proteins. Advances in technology will undeniable lead us to more answers on the subject {{#pmid:22230617|PMID22230617}}.<br /> <br /> ===Embryonic origins===<br /> ----<br /> https://www.ncbi.nlm.nih.gov/books/NBK10065/<br /> <br /> The adrenal gland is made up of the adrenal cortex and adrenal medulla, which both have different embryonic origins. The adrenal medulla arises from the neural crest tissue, found near the level of the coeliac plexus & sympathetic ganglion {{#pmid:16124976|PMID16124976}}. Specifically, this neural crest tissue comes from the trunk neural crest cells (see above figure to determine the approximate location in an embryo) <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> The trunk neural crest coordinates the development of the endocrine system, secretory cells, the peripheral nervous system and, to some degree, skeletal development, as well as innervation of the intestine {{#pmid: 28287247|PMID 28287247}}. The trunk neural cells arise caudally and follow three migratory pathways {{#pmid:20399766|PMID20399766}}.<br /> <br /> - A dorsolateral pathway (between ectoderm and somites)<br /> - A ventrolateral pathway (through the somites)<br /> - A ventromedial pathway (between neural tube and posterior schlerotome){{#pmid:20399766|PMID20399766}}.<br /> <br /> Somites are collections of paraxial mesoderm that are located from the head to the tail of the embryo, forming skeletal structures, cartilages and tendons of the back <ref name="Larsen">{{cite book|last1=Larsen|first1=William J.|title=Human embryology|date=2001|publisher=Churchill Livingstone|location=Philadelphia, Pa.|isbn=0-443-06583-7|pages=53–86|edition=3.}}</ref>.<br /> <br /> ===Developmental time course===<br /> ----<br /> <br /> [[File:Adrenal_Medulla_Developmental_Timeline.jpg|right|thumb|500px]]<br /> <br /> The adrenal gland has two distinct sections, the cortex and the medulla, both with different embryonic origins. The cortex accounts for 90% of the adrenal glands and arises from intermediate mesoderm. The medulla only accounts for 10% of the adult adrenal glands, however it has neural crest embryonic origin. The medulla consists of chromaffinoblast cells which are migrant neuroblast cells from the neural crest, therefore the adrenal medulla is a component of the sympathetic nervous system.{{#pmid:21175739|PMID21175739}} Neural crest cells replicate in week 7 and begin to differentiate in week 8, the cells then migrate to the developing adrenal gland in week 9 of development.{{#pmid:25255746|PMID25255746}}{{#pmid:18279781|PMID18279781}} The neural crest cells infiltrate the cortex and the chromaffin cells are scattered islands in the cortex.{{#pmid:23354096|PMID23354096}} Throughout development the cells will become more compact in the centre of the gland, during this period of development the adrenal gland is growing rapidly. The gland is abnormally large until the second trimester and the medulla is much thicker prenatally.{{#pmid:18279781|PMID18279781}}{{#pmid:21175739|PMID21175739}}<br /> <br /> ===Developmental/adult function===<br /> ----<br /> ===Tissue and Organ structure===<br /> <br /> <br /> ====Normal Structure and Function of the Adrenal Medulla====<br /> <br /> The cells of the adrenal medulla are derived from the neural crest as opposed to the mesodermal origins of the cortex. The medulla contains secretory cells called chromaffin cells, due to the agents they produce when oxidised, such as chromate. These cells secrete epinephrine and norepinephrine in response to various substances such as acetylcholine.<br /> <br /> There are three types of cells in the adult adrenal medulla: <br /> 1) Epinephrine cells<br /> <br /> 2) Norepinephrine cells <br /> <br /> 3) Small granule-containing cells (SGCs)<br /> <br /> These cells also produce various other peptides such as substance P and neurotensin. The adrenal medulla also contains presynaptic sympathetic ganglion cells. {{#pmid:1694230|PMID1694230}}<br /> <br /> ====Related Anatomy====<br /> <br /> The tissue and organ structure of the adrenal medulla should be understood with regard to its specialised function within the sympathetic nervous system. <br /> <br /> The medullary region of the adrenal glands is tasked with the endocrine secretions of adrenaline and nor-adrenaline in response to environmental stressors that are signalled for by the sympathetic nervous system. That is, the secretion of fight-or-flight response hormones in order to restrict vasculature to the trunk and increase vascular activity in the peripheral musculature.<br /> <br /> The adrenal glands are supplied by several branches of the great vessels in the abdominal cavity. The secreted catecholamines in the medulla are directly able to pass to the blood stream this way.<br /> <br /> These adrenal glands and their contents are retroperitoneal in the adult and varied in shape, with the left often being semilunar and right being pyramidal. Nervous supply of the adrenal glands is achieved by contributions from the splanchnic nerves of the celiac plexus.<br /> <br /> <br /> ====Role of the Adrenal Medulla====<br /> <br /> Understanding the biochemistry of catecholamines is necessary to see how the adrenal medulla is designed in the stages of embryology and how it is suited for life in the neonate and adult. <br /> <br /> The epinephrine and norepinephrine in the neonate and adult work by primarily changing the osmoregulatory state of vasculature in organs. With the exclusion of their neuromodulatory and neurotransmitter functions, epinephrine and norepinephrine are mainly tasked with the control of sympathetic and parasympathetic supplies. <br /> <br /> Norepinephrine is a constrictor of peripheral vasculature by antagonising the action of surface receptors expressed on the endothelium of blood vessels, specifically Alpha-1 and Alpha-2 receptors, such that vascular resistance increases. <br /> <br /> Epinephrine is both a vasoconstrictor and vasodilator, depending on what receptors it attaches to. As a non-selective adrenergic agonist, it acts on Alpha-1, Alpha-2, Beta-1, Beta-2 and Beta-3 receptors that are found throughout the body's tissues, yielding many different physiological responses.<br /> <br /> <br /> [[File:Dd.jpg|500px|thumb|right|Adult Adrenal Glands in situ]] <br /> ----<br /> <br /> ===Molecular mechanisms/factors/genes===<br /> ----<br /> <br /> ====Genes and Transcription Factors Involved with the Adrenal Medulla's Development====<br /> <br /> Members of the SOX (SRY-Box) gene family have multiple key contributors to Neural Crest in the Adrenal Medulla.<br /> <br /> Mouse models have demonstrated that SOX-10 knock-outs (mice whose DNA has been engineered to not express SOX-10) do not have an adrenal medulla. There has also been suggestion that SOX-8,9 and 10 are all strongly related to the migratory patterning of neural crest cells to the developing adrenal glands.<br /> <br /> The TH gene (for Tyrosine Hydroxylase) encodes the aforementioned enzyme in the adrenal medulla and central nervous system. Tyrosine Hydroxylase is crucial in biochemical pathways and cascades for the synthesis of catecholamines and other CNS neurotransmitters. The conversion from L-Tyrosine to L-DOPA is dependent upon the catalytic action of Tyrosine Hydroxylase. From there, L-DOPA can make Dopamine and eventually Epinephrine and Norepinephrine as well. <br /> <br /> [[File:Catecholamine_Synthesis.jpg|500px|thumb|right|Cascade of Catecholamine Synthesis]]<br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2291442/<br /> https://www.ncbi.nlm.nih.gov/pubmed/19396395<br /> <br /> ===Abnormalities/abnormal development===<br /> ----<br /> ===Animal models===<br /> ----<br /> Animal models are an integral part of research in embryology. In particular due to the moral concerns regarding the use of humans in scientific research. As a result different animals are used as substitutes to simulate the same environments and hope to achieve results that would also be able to represent humans as well. Prenatal adrenal gland development has been described in a number of scientific reports dating from the 1900s to studies in more recent years. These involved a variety of animal models such as ox, sheep, swine and most commonly mice. <br /> <br /> ====Chromaffin cells =(in rat models)====<br /> There has been extensive research conducted into the adrenal chromaffin cells and their embryological developments. As explained above nueral crest cells are pluripotent meaning they are able to differentiate into multiple different cells. The neural crest cells give rise to chromaffin cells of the adrenal medulla.<br /> <br /> To study the formation process of the adrenal medulla in the embryonic period, we visualized chromaffin cells of rat embryos at 13 to 17 days of gestation using anti-tyrosine hydroxylase (TH) antiserum, and created three-dimensional images from serial tissue sections. Between 13 and 15 days of gestation, TH-positive cells (chromaffin cells) migrated from a group of TH-positive cells present dorsal to the adrenal primordium via the medial cranial end of the adrenal primordium into the adrenal primordium. At or after 16 days of gestation, the adrenal capsule was formed except on the ventral aspect of the cranial end of the adrenal gland, from which TH-positive cells penetrated into the adrenal gland.(Pubmed: 15240937) <br /> <br /> Ahonen suggested that some neural crest cells continue migration from the chain ganglia to the lateral sides of aorta, where they form the perirenal ganglia and adrenal medulla, and finally to the ventral side of the aorta to form the preaortic sympathetic tissue. However, that report only showed the several transverse sections of the fetal trunk for the a demonstration of the migration route of neural crest cells. In this study, using three dimensional reconstructed images, we aimed to observe how TH-labeled chromaffin cells penetrate into the adrenal anlage to form the adrenal medulla and whether the migration route of TH - positive cells from the adrenal connects the preaortic sympathetic ganglia <br /> (M.Yamato, R. Yanai, K. Arishima, 2004) <br /> <br /> Prenatal adrenal gland development has been described in numerous published reports covering a wide variety of species, including the ox (Katznelson, 1966; Wrobel and Suss, 1999), sheep (Davies, 1950; Wintour et al., 1975; Upadhyay and Zamboni, 1982; Naaman‐Reperant and Durand, 1997; Grino, 2004), swine (Sokolov et al., 2006) and mouse (Waring, 1935; Ikeda et al., 1994; Sass, 1996; Nyska and Maronpot, 1999; Bland et al., 2003; Val et al., 2007). Adrenal gland development also has been extensively described for humans as well (Kolliker, 1879; Minot, 1892; Zuckerkandl, 1912; Wieman, 1920; Ikeda et al., 1981; Langlois et al., 2002; Hanley and Arit, 2006).<br /> <br /> https://www.sciencedirect.com/science/article/pii/S0925477302004550<br /> http://dev.biologists.org/content/develop/126/13/2935.full.pdf<br /> <br /> ===Current research (labs)===<br /> ----<br /> The findings presented until now have focused on the mechanisms controlling migration along the dorsolateral path. In comparison, our understanding of the mechanisms controlling NCC migration along the ventral path are complicated by the fact that this population comprises multiple precursors that form different derivatives in distinct regions of the embryo. For example, ventrally migrating NCCs either stop within the sclerotome in close association with the neural tube to form neurons and glia of the sensory nervous system (i.e. the dorsal root ganglia [DRG]), while other NCCs continue to migrate further ventrally to form the autonomic nervous system (i.e. sympathetic ganglia and chromaffin cells of the adrenal gland)<br /> <br /> Adrenomedullary chromaffin cells are catecholamine (CA)-producing cells originating from trunk neural crest (NC) via sympathoadrenal progenitors (SAPs). We generated NC and SAPs from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) in vitro via BMP2/FGF2 exposure, ascertained by qPCR and immunoexpression of SOX10, ASCL1, TFAP2α, and PHOX2B, and by fluorescence-activated cell sorting selection for p75NTR and GD2, and confirmed their trunk-like HOX gene expression. We showed that continuing BMP4 and curtailing FGF2 in vitro, augmented with corticosteroid mimetic, induced these cells to upregulate the chromaffin cell-specific marker PNMT and other CA synthesis and storage markers, and we demonstrated noradrenaline and adrenaline by Faglu and high-performance liquid chromatography. We showed these human cells' SAP-like property of migration and differentiation into cells expressing chromaffin cell markers by implanting them into avian embryos in vivo and in chorio-allantoic membrane grafts. These cells have the potential for investigating differentiation of human chromaffin cells and for modeling diseases involving this cell type.<br /> <br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768882/<br /> <br /> ===Glossary===<br /> ----<br /> ===Reference list===</div>

Z5091101 https://embryology.med.unsw.edu.au/embryology/index.php?title=2018_Group_Project_1&diff=356541 2018 Group Project 1 2018-10-09T07:50:29Z

<p>Z5091101: /* Embryonic origins */</p> <hr /> <div>=The Contribution of Neural Crest Cells to the Adrenal Medulla=<br /> ----<br /> {{2018ANAT2341ProjectHeader}}<br /> <br /> <br /> ===Introduction===<br /> [[User:Z5014972|Z5014972]] ([[User talk:Z5014972|talk]]) 12:47, 14 August 2018 (AEST)z5014972 <br /> good review article https://link.springer.com/article/10.1007%2Fs12022-009-9070-6<br /> ----<br /> <br /> <br /> The neural crest of an embryo differentiates and migrates to form various components of the body. One of these tissues is the medulla of the adrenal gland which is involved in the production of adrenalin and noradrenalin. This project will comprehensively outline the history of neural crest research, the embryonic developmental time course, tissue and organ structure, molecular mechanisms, abnormalities, animal models and current research.<br /> <br /> ===History===<br /> ----<br /> '''Describing the neural crest'''<br /> [[File:Wilhelm_His_History_Wilhelm.jpeg|left|230px|thumb|Wilhelm His]]<br /> The "neural crest" is a structure in the embryo and is the junction between the neural and epidermal ectoderm. It is exclusive to vertebrates and forms a range of structures{{#pmid:22230617|PMID22230617}}. The neural crest contributes a large number of cells of varying structure and function that directly or indirectly contribute to the development of tissues and organs within the body {{#pmid:19179766|PMID19179766}}. In 1868, the neural crest cells were first identified in a chick embryo as a collection of cells known as "Zwischenstrang" by Professor Wilhelm His {{#pmid:22820859|PMID22820859}}. Wilhelm His was among the first to provide an explanation for the mechanics governing the developing embryo as well as the physiology and the organs that the differing germinal regions would eventually give rise to. In 1878, the term neural ridge was used to describe this collection of cells but the term neural crest was later coined by Arthur Milnes Marshall in 1879 in a paper he worked on disseminating the knowledge from his research on the development of cranial nerves in chicken embryos. {{#pmid:19179766|PMID19179766}}.<br /> [[File:NC Location.jpg|left|450px|thumb|The neural crest]]<br /> <br /> '''1890s-1950s'''<br /> The neural crest is the point of origin for spinal/cranial ganglia and neurons. This theory received little criticism and was not contested much by other researchers prior to the 1890s. This is owing to the fact that the neural crest is quite closely related to the neural tube and thus this relationship makes sense. This discovery was made by His and Marshall, however, they found this out independently of one another.In the 1890s, Julia Platt, claimed that odontoblasts as well as the cartilages forming the facial and pharyngeal arch skeletons came from the ectoderm. This created much debate and was contested by many{{#pmid:22820859|PMID22820859}}. <br /> <br /> This is because this theory completely contradicted the germ-layer theory, whereby skeletal tissues originate at the mesoderm and not the ectoderm. The controversies this finding created brought about a slowing down of research, as demonstrated by a gap of almost 40 years between the theory that skeletal tissues originating from the neural crest. Today, it is known that the neural crest does indeed play a role in the development of the skeleton in vertebrates, particularly, the cranial neural crest. Although these studies were occurring, the focus was still primarily on researching pigment cells and ganglia of the spine up until the 1950s, when Sven Hörstadius' major work on the neural crest was published, titled "The Neural Crest: Its properties and derivatives in the light of experimental research". This work focused on experimental data tracing the development of the cartilaginous skeleton derived from the neural crest {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1960s - 1970s'''<br /> In the 1960s, the migration patterns of neural crest cells were studied in avian embryos (birds). This was a shift from studying the embryos of amphibians. This was inspired by studies conducted in the 1960s on neural crest cells migrating from the brain and spinal cord, known as trunk and cranial neural crest cells {{#pmid:19179766|PMID19179766}}. The cranial neural crest eventually becomes the bones, cartilage and connective tissues forming the foundation of the face, ears and teeth. The trunk neural crest cells can either become melanocytes or can migrate into sclerotomes which are later contributors to the cartilage of the spine and the dorsal root ganglia {{#pmid:22820859|PMID22820859}}. The cells in the trunk neural crest that migrate vertically become the sympathetic ganglia, the nerves proximal to the aorta and the adrenal medulla <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. In the 1970s many detailed maps signifying the pathways of many of the neural crest cells appeared as well as an understanding that the environment in which the neural crest cells are found plays a major role in their final development as well as the occurrences of abnormalities in the fetus {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1980s - 21st century'''<br /> [[File:Regions_of_NC_Cells.jpg|left|Neural crest regions|thumb]]<br /> From the 1980s-1990s, the causative agent of organ transformation from one to another (homeotic patterning), as well as the Hox genes which regulate the axis of most symmetrical animal embryos were founded and studied. The neural crest, which previously was divided into the cranial and trunk regions, was now further divided into the vagal and sacral neural crest, the cardiac neural crest and the cephalic neural crest {{#pmid:19179766|PMID19179766}}. The vagal & sacral neural crest gives rise to the parasympathetic ganglia found in the gut. Without these ganglia, peristalsis, is not possible <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. The cardiac neural crest contributes to the valves, septa and major blood vessels of the heart, as well as connective tissues and cartilage{{#pmid:19179766|PMID19179766}}. This is important for the structure of the heart as well as its overall function, enabling it to move blood around the body efficiently as well as keep pulmonary and aortic circulation separated <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> <br /> <br /> Today, knowledge of the neural crest cells, their migration patterns, modes of differentiation, derivatives and apoptosis (cell death) are being studied extensively. This is being done on a comparative basis between different organisms, to add further evidence for evolution {{#pmid:19179766|PMID19179766}}. The neural crest is definitely forging a "crest" between the fields of developmental and evolutionary biology, as it is a structure '''shared exclusively by all vertebrates'''. Invertebrates do not derive their specialised cells from the neural crest as they do not have one, rather, they derive these from the endomesoderm {{#pmid:22230617|PMID22230617}}.<br /> <br /> '''Future directions'''<br /> <br /> Since its discovery by His, the neural crest field has made great progress, from studies performed on the structure, to analysis of the molecules and whether certain aspects of the neural crest are specific to a single species of organism, or to all vertebrates collectively. Future work on the cranial neural crest needs to be done as well as identifying and categorising the networks responsible for the proliferation and death of cells, as well as how the cells move and migrate, as well as the gene regulatory networks (GRNs) that regulate the synthesis of proteins. Advances in technology will undeniable lead us to more answers on the subject {{#pmid:22230617|PMID22230617}}.<br /> <br /> ===Embryonic origins===<br /> ----<br /> https://www.ncbi.nlm.nih.gov/books/NBK10065/<br /> <br /> The adrenal gland is made up of the adrenal cortex and adrenal medulla, which both have different embryonic origins. The adrenal medulla arises from the neural crest tissue, found near the level of the coeliac plexus & sympathetic ganglion {{#pmid:16124976|PMID16124976}}. Specifically, this neural crest tissue comes from the trunk neural crest cells (see above figure to determine the approximate location in an embryo) <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> The trunk neural crest coordinates the development of the endocrine system, secretory cells, the peripheral nervous system and, to some degree, skeletal development, as well as innervation of the intestine {{#pmid: 28287247|PMID 28287247}}. The trunk neural cells arise caudally and follow three migratory pathways {{pmid:#20399766|PMID20399766}}:<br /> <br /> - A dorsolateral pathway<br /> - A ventrolateral pathway<br /> - A ventromedial pathway {{#pmid:20399766|PMID20399766}}.<br /> <br /> ===Developmental time course===<br /> ----<br /> <br /> [[File:Adrenal_Medulla_Developmental_Timeline.jpg|right|thumb|500px]]<br /> <br /> The adrenal gland has two distinct sections, the cortex and the medulla, both with different embryonic origins. The cortex accounts for 90% of the adrenal glands and arises from intermediate mesoderm. The medulla only accounts for 10% of the adult adrenal glands, however it has neural crest embryonic origin. The medulla consists of chromaffinoblast cells which are migrant neuroblast cells from the neural crest, therefore the adrenal medulla is a component of the sympathetic nervous system.{{#pmid:21175739|PMID21175739}} Neural crest cells replicate in week 7 and begin to differentiate in week 8, the cells then migrate to the developing adrenal gland in week 9 of development.{{#pmid:25255746|PMID25255746}}{{#pmid:18279781|PMID18279781}} The neural crest cells infiltrate the cortex and the chromaffin cells are scattered islands in the cortex.{{#pmid:23354096|PMID23354096}} Throughout development the cells will become more compact in the centre of the gland, during this period of development the adrenal gland is growing rapidly. The gland is abnormally large until the second trimester and the medulla is much thicker prenatally.{{#pmid:18279781|PMID18279781}}{{#pmid:21175739|PMID21175739}}<br /> <br /> ===Developmental/adult function===<br /> ----<br /> ===Tissue and Organ structure===<br /> <br /> <br /> ====Normal Structure and Function of the Adrenal Medulla====<br /> <br /> The cells of the adrenal medulla are derived from the neural crest as opposed to the mesodermal origins of the cortex. The medulla contains secretory cells called chromaffin cells, due to the agents they produce when oxidised, such as chromate. These cells secrete epinephrine and norepinephrine in response to various substances such as acetylcholine.<br /> <br /> There are three types of cells in the adult adrenal medulla: <br /> 1) Epinephrine cells<br /> <br /> 2) Norepinephrine cells <br /> <br /> 3) Small granule-containing cells (SGCs)<br /> <br /> These cells also produce various other peptides such as substance P and neurotensin. The adrenal medulla also contains presynaptic sympathetic ganglion cells. {{#pmid:1694230|PMID1694230}}<br /> <br /> ====Related Anatomy====<br /> <br /> The tissue and organ structure of the adrenal medulla should be understood with regard to its specialised function within the sympathetic nervous system. <br /> <br /> The medullary region of the adrenal glands is tasked with the endocrine secretions of adrenaline and nor-adrenaline in response to environmental stressors that are signalled for by the sympathetic nervous system. That is, the secretion of fight-or-flight response hormones in order to restrict vasculature to the trunk and increase vascular activity in the peripheral musculature.<br /> <br /> The adrenal glands are supplied by several branches of the great vessels in the abdominal cavity. The secreted catecholamines in the medulla are directly able to pass to the blood stream this way.<br /> <br /> These adrenal glands and their contents are retroperitoneal in the adult and varied in shape, with the left often being semilunar and right being pyramidal. Nervous supply of the adrenal glands is achieved by contributions from the splanchnic nerves of the celiac plexus.<br /> <br /> <br /> ====Role of the Adrenal Medulla====<br /> <br /> Understanding the biochemistry of catecholamines is necessary to see how the adrenal medulla is designed in the stages of embryology and how it is suited for life in the neonate and adult. <br /> <br /> The epinephrine and norepinephrine in the neonate and adult work by primarily changing the osmoregulatory state of vasculature in organs. With the exclusion of their neuromodulatory and neurotransmitter functions, epinephrine and norepinephrine are mainly tasked with the control of sympathetic and parasympathetic supplies. <br /> <br /> Norepinephrine is a constrictor of peripheral vasculature by antagonising the action of surface receptors expressed on the endothelium of blood vessels, specifically Alpha-1 and Alpha-2 receptors, such that vascular resistance increases. <br /> <br /> Epinephrine is both a vasoconstrictor and vasodilator, depending on what receptors it attaches to. As a non-selective adrenergic agonist, it acts on Alpha-1, Alpha-2, Beta-1, Beta-2 and Beta-3 receptors that are found throughout the body's tissues, yielding many different physiological responses.<br /> <br /> <br /> [[File:Dd.jpg|500px|thumb|right|Adult Adrenal Glands in situ]] <br /> ----<br /> <br /> ===Molecular mechanisms/factors/genes===<br /> ----<br /> <br /> ====Genes and Transcription Factors Involved with the Adrenal Medulla's Development====<br /> <br /> Members of the SOX (SRY-Box) gene family have multiple key contributors to Neural Crest in the Adrenal Medulla.<br /> <br /> Mouse models have demonstrated that SOX-10 knock-outs (mice whose DNA has been engineered to not express SOX-10) do not have an adrenal medulla. There has also been suggestion that SOX-8,9 and 10 are all strongly related to the migratory patterning of neural crest cells to the developing adrenal glands.<br /> <br /> The TH gene (for Tyrosine Hydroxylase) encodes the aforementioned enzyme in the adrenal medulla and central nervous system. Tyrosine Hydroxylase is crucial in biochemical pathways and cascades for the synthesis of catecholamines and other CNS neurotransmitters. The conversion from L-Tyrosine to L-DOPA is dependent upon the catalytic action of Tyrosine Hydroxylase. From there, L-DOPA can make Dopamine and eventually Epinephrine and Norepinephrine as well. <br /> <br /> [[File:Catecholamine_Synthesis.jpg|500px|thumb|right|Cascade of Catecholamine Synthesis]]<br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2291442/<br /> https://www.ncbi.nlm.nih.gov/pubmed/19396395<br /> <br /> ===Abnormalities/abnormal development===<br /> ----<br /> ===Animal models===<br /> ----<br /> Animal models are an integral part of research in embryology. In particular due to the moral concerns regarding the use of humans in scientific research. As a result different animals are used as substitutes to simulate the same environments and hope to achieve results that would also be able to represent humans as well. Prenatal adrenal gland development has been described in a number of scientific reports dating from the 1900s to studies in more recent years. These involved a variety of animal models such as ox, sheep, swine and most commonly mice. <br /> <br /> ====Chromaffin cells =(in rat models)====<br /> There has been extensive research conducted into the adrenal chromaffin cells and their embryological developments. As explained above nueral crest cells are pluripotent meaning they are able to differentiate into multiple different cells. The neural crest cells give rise to chromaffin cells of the adrenal medulla.<br /> <br /> To study the formation process of the adrenal medulla in the embryonic period, we visualized chromaffin cells of rat embryos at 13 to 17 days of gestation using anti-tyrosine hydroxylase (TH) antiserum, and created three-dimensional images from serial tissue sections. Between 13 and 15 days of gestation, TH-positive cells (chromaffin cells) migrated from a group of TH-positive cells present dorsal to the adrenal primordium via the medial cranial end of the adrenal primordium into the adrenal primordium. At or after 16 days of gestation, the adrenal capsule was formed except on the ventral aspect of the cranial end of the adrenal gland, from which TH-positive cells penetrated into the adrenal gland.(Pubmed: 15240937) <br /> <br /> Ahonen suggested that some neural crest cells continue migration from the chain ganglia to the lateral sides of aorta, where they form the perirenal ganglia and adrenal medulla, and finally to the ventral side of the aorta to form the preaortic sympathetic tissue. However, that report only showed the several transverse sections of the fetal trunk for the a demonstration of the migration route of neural crest cells. In this study, using three dimensional reconstructed images, we aimed to observe how TH-labeled chromaffin cells penetrate into the adrenal anlage to form the adrenal medulla and whether the migration route of TH - positive cells from the adrenal connects the preaortic sympathetic ganglia <br /> (M.Yamato, R. Yanai, K. Arishima, 2004) <br /> <br /> Prenatal adrenal gland development has been described in numerous published reports covering a wide variety of species, including the ox (Katznelson, 1966; Wrobel and Suss, 1999), sheep (Davies, 1950; Wintour et al., 1975; Upadhyay and Zamboni, 1982; Naaman‐Reperant and Durand, 1997; Grino, 2004), swine (Sokolov et al., 2006) and mouse (Waring, 1935; Ikeda et al., 1994; Sass, 1996; Nyska and Maronpot, 1999; Bland et al., 2003; Val et al., 2007). Adrenal gland development also has been extensively described for humans as well (Kolliker, 1879; Minot, 1892; Zuckerkandl, 1912; Wieman, 1920; Ikeda et al., 1981; Langlois et al., 2002; Hanley and Arit, 2006).<br /> <br /> https://www.sciencedirect.com/science/article/pii/S0925477302004550<br /> http://dev.biologists.org/content/develop/126/13/2935.full.pdf<br /> <br /> ===Current research (labs)===<br /> ----<br /> The findings presented until now have focused on the mechanisms controlling migration along the dorsolateral path. In comparison, our understanding of the mechanisms controlling NCC migration along the ventral path are complicated by the fact that this population comprises multiple precursors that form different derivatives in distinct regions of the embryo. For example, ventrally migrating NCCs either stop within the sclerotome in close association with the neural tube to form neurons and glia of the sensory nervous system (i.e. the dorsal root ganglia [DRG]), while other NCCs continue to migrate further ventrally to form the autonomic nervous system (i.e. sympathetic ganglia and chromaffin cells of the adrenal gland)<br /> <br /> Adrenomedullary chromaffin cells are catecholamine (CA)-producing cells originating from trunk neural crest (NC) via sympathoadrenal progenitors (SAPs). We generated NC and SAPs from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) in vitro via BMP2/FGF2 exposure, ascertained by qPCR and immunoexpression of SOX10, ASCL1, TFAP2α, and PHOX2B, and by fluorescence-activated cell sorting selection for p75NTR and GD2, and confirmed their trunk-like HOX gene expression. We showed that continuing BMP4 and curtailing FGF2 in vitro, augmented with corticosteroid mimetic, induced these cells to upregulate the chromaffin cell-specific marker PNMT and other CA synthesis and storage markers, and we demonstrated noradrenaline and adrenaline by Faglu and high-performance liquid chromatography. We showed these human cells' SAP-like property of migration and differentiation into cells expressing chromaffin cell markers by implanting them into avian embryos in vivo and in chorio-allantoic membrane grafts. These cells have the potential for investigating differentiation of human chromaffin cells and for modeling diseases involving this cell type.<br /> <br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768882/<br /> <br /> ===Glossary===<br /> ----<br /> ===Reference list===</div>

Z5091101 https://embryology.med.unsw.edu.au/embryology/index.php?title=2018_Group_Project_1&diff=356539 2018 Group Project 1 2018-10-09T07:49:04Z

<p>Z5091101: /* Embryonic origins */</p> <hr /> <div>=The Contribution of Neural Crest Cells to the Adrenal Medulla=<br /> ----<br /> {{2018ANAT2341ProjectHeader}}<br /> <br /> <br /> ===Introduction===<br /> [[User:Z5014972|Z5014972]] ([[User talk:Z5014972|talk]]) 12:47, 14 August 2018 (AEST)z5014972 <br /> good review article https://link.springer.com/article/10.1007%2Fs12022-009-9070-6<br /> ----<br /> <br /> <br /> The neural crest of an embryo differentiates and migrates to form various components of the body. One of these tissues is the medulla of the adrenal gland which is involved in the production of adrenalin and noradrenalin. This project will comprehensively outline the history of neural crest research, the embryonic developmental time course, tissue and organ structure, molecular mechanisms, abnormalities, animal models and current research.<br /> <br /> ===History===<br /> ----<br /> '''Describing the neural crest'''<br /> [[File:Wilhelm_His_History_Wilhelm.jpeg|left|230px|thumb|Wilhelm His]]<br /> The "neural crest" is a structure in the embryo and is the junction between the neural and epidermal ectoderm. It is exclusive to vertebrates and forms a range of structures{{#pmid:22230617|PMID22230617}}. The neural crest contributes a large number of cells of varying structure and function that directly or indirectly contribute to the development of tissues and organs within the body {{#pmid:19179766|PMID19179766}}. In 1868, the neural crest cells were first identified in a chick embryo as a collection of cells known as "Zwischenstrang" by Professor Wilhelm His {{#pmid:22820859|PMID22820859}}. Wilhelm His was among the first to provide an explanation for the mechanics governing the developing embryo as well as the physiology and the organs that the differing germinal regions would eventually give rise to. In 1878, the term neural ridge was used to describe this collection of cells but the term neural crest was later coined by Arthur Milnes Marshall in 1879 in a paper he worked on disseminating the knowledge from his research on the development of cranial nerves in chicken embryos. {{#pmid:19179766|PMID19179766}}.<br /> [[File:NC Location.jpg|left|450px|thumb|The neural crest]]<br /> <br /> '''1890s-1950s'''<br /> The neural crest is the point of origin for spinal/cranial ganglia and neurons. This theory received little criticism and was not contested much by other researchers prior to the 1890s. This is owing to the fact that the neural crest is quite closely related to the neural tube and thus this relationship makes sense. This discovery was made by His and Marshall, however, they found this out independently of one another.In the 1890s, Julia Platt, claimed that odontoblasts as well as the cartilages forming the facial and pharyngeal arch skeletons came from the ectoderm. This created much debate and was contested by many{{#pmid:22820859|PMID22820859}}. <br /> <br /> This is because this theory completely contradicted the germ-layer theory, whereby skeletal tissues originate at the mesoderm and not the ectoderm. The controversies this finding created brought about a slowing down of research, as demonstrated by a gap of almost 40 years between the theory that skeletal tissues originating from the neural crest. Today, it is known that the neural crest does indeed play a role in the development of the skeleton in vertebrates, particularly, the cranial neural crest. Although these studies were occurring, the focus was still primarily on researching pigment cells and ganglia of the spine up until the 1950s, when Sven Hörstadius' major work on the neural crest was published, titled "The Neural Crest: Its properties and derivatives in the light of experimental research". This work focused on experimental data tracing the development of the cartilaginous skeleton derived from the neural crest {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1960s - 1970s'''<br /> In the 1960s, the migration patterns of neural crest cells were studied in avian embryos (birds). This was a shift from studying the embryos of amphibians. This was inspired by studies conducted in the 1960s on neural crest cells migrating from the brain and spinal cord, known as trunk and cranial neural crest cells {{#pmid:19179766|PMID19179766}}. The cranial neural crest eventually becomes the bones, cartilage and connective tissues forming the foundation of the face, ears and teeth. The trunk neural crest cells can either become melanocytes or can migrate into sclerotomes which are later contributors to the cartilage of the spine and the dorsal root ganglia {{#pmid:22820859|PMID22820859}}. The cells in the trunk neural crest that migrate vertically become the sympathetic ganglia, the nerves proximal to the aorta and the adrenal medulla <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. In the 1970s many detailed maps signifying the pathways of many of the neural crest cells appeared as well as an understanding that the environment in which the neural crest cells are found plays a major role in their final development as well as the occurrences of abnormalities in the fetus {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1980s - 21st century'''<br /> [[File:Regions_of_NC_Cells.jpg|left|Neural crest regions|thumb]]<br /> From the 1980s-1990s, the causative agent of organ transformation from one to another (homeotic patterning), as well as the Hox genes which regulate the axis of most symmetrical animal embryos were founded and studied. The neural crest, which previously was divided into the cranial and trunk regions, was now further divided into the vagal and sacral neural crest, the cardiac neural crest and the cephalic neural crest {{#pmid:19179766|PMID19179766}}. The vagal & sacral neural crest gives rise to the parasympathetic ganglia found in the gut. Without these ganglia, peristalsis, is not possible <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. The cardiac neural crest contributes to the valves, septa and major blood vessels of the heart, as well as connective tissues and cartilage{{#pmid:19179766|PMID19179766}}. This is important for the structure of the heart as well as its overall function, enabling it to move blood around the body efficiently as well as keep pulmonary and aortic circulation separated <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> <br /> <br /> Today, knowledge of the neural crest cells, their migration patterns, modes of differentiation, derivatives and apoptosis (cell death) are being studied extensively. This is being done on a comparative basis between different organisms, to add further evidence for evolution {{#pmid:19179766|PMID19179766}}. The neural crest is definitely forging a "crest" between the fields of developmental and evolutionary biology, as it is a structure '''shared exclusively by all vertebrates'''. Invertebrates do not derive their specialised cells from the neural crest as they do not have one, rather, they derive these from the endomesoderm {{#pmid:22230617|PMID22230617}}.<br /> <br /> '''Future directions'''<br /> <br /> Since its discovery by His, the neural crest field has made great progress, from studies performed on the structure, to analysis of the molecules and whether certain aspects of the neural crest are specific to a single species of organism, or to all vertebrates collectively. Future work on the cranial neural crest needs to be done as well as identifying and categorising the networks responsible for the proliferation and death of cells, as well as how the cells move and migrate, as well as the gene regulatory networks (GRNs) that regulate the synthesis of proteins. Advances in technology will undeniable lead us to more answers on the subject {{#pmid:22230617|PMID22230617}}.<br /> <br /> ===Embryonic origins===<br /> ----<br /> https://www.ncbi.nlm.nih.gov/books/NBK10065/<br /> <br /> The adrenal gland is made up of the adrenal cortex and adrenal medulla, which both have different embryonic origins. The adrenal medulla arises from the neural crest tissue, found near the level of the coeliac plexus & sympathetic ganglion {{#pmid:16124976|PMID16124976}}. Specifically, this neural crest tissue comes from the trunk neural crest cells (see above figure to determine the approximate location in an embryo) <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> The trunk neural crest coordinates the development of the endocrine system, secretory cells, the peripheral nervous system and, to some degree, skeletal development, as well as innervation of the intestine {{#pmid: 28287247|PMID 28287247}}. The trunk neural cells arise caudally and follow three migratory pathways {{pmid:#20399766|PMID20399766}}:<br /> <br /> - A dorsolateral pathway<br /> - A ventrolateral pathway<br /> - A ventromedial pathway {{pmid:#2914176|PMID2914176}}<br /> <br /> ===Developmental time course===<br /> ----<br /> <br /> [[File:Adrenal_Medulla_Developmental_Timeline.jpg|right|thumb|500px]]<br /> <br /> The adrenal gland has two distinct sections, the cortex and the medulla, both with different embryonic origins. The cortex accounts for 90% of the adrenal glands and arises from intermediate mesoderm. The medulla only accounts for 10% of the adult adrenal glands, however it has neural crest embryonic origin. The medulla consists of chromaffinoblast cells which are migrant neuroblast cells from the neural crest, therefore the adrenal medulla is a component of the sympathetic nervous system.{{#pmid:21175739|PMID21175739}} Neural crest cells replicate in week 7 and begin to differentiate in week 8, the cells then migrate to the developing adrenal gland in week 9 of development.{{#pmid:25255746|PMID25255746}}{{#pmid:18279781|PMID18279781}} The neural crest cells infiltrate the cortex and the chromaffin cells are scattered islands in the cortex.{{#pmid:23354096|PMID23354096}} Throughout development the cells will become more compact in the centre of the gland, during this period of development the adrenal gland is growing rapidly. The gland is abnormally large until the second trimester and the medulla is much thicker prenatally.{{#pmid:18279781|PMID18279781}}{{#pmid:21175739|PMID21175739}}<br /> <br /> ===Developmental/adult function===<br /> ----<br /> ===Tissue and Organ structure===<br /> <br /> <br /> ====Normal Structure and Function of the Adrenal Medulla====<br /> <br /> The cells of the adrenal medulla are derived from the neural crest as opposed to the mesodermal origins of the cortex. The medulla contains secretory cells called chromaffin cells, due to the agents they produce when oxidised, such as chromate. These cells secrete epinephrine and norepinephrine in response to various substances such as acetylcholine.<br /> <br /> There are three types of cells in the adult adrenal medulla: <br /> 1) Epinephrine cells<br /> <br /> 2) Norepinephrine cells <br /> <br /> 3) Small granule-containing cells (SGCs)<br /> <br /> These cells also produce various other peptides such as substance P and neurotensin. The adrenal medulla also contains presynaptic sympathetic ganglion cells. {{#pmid:1694230|PMID1694230}}<br /> <br /> ====Related Anatomy====<br /> <br /> The tissue and organ structure of the adrenal medulla should be understood with regard to its specialised function within the sympathetic nervous system. <br /> <br /> The medullary region of the adrenal glands is tasked with the endocrine secretions of adrenaline and nor-adrenaline in response to environmental stressors that are signalled for by the sympathetic nervous system. That is, the secretion of fight-or-flight response hormones in order to restrict vasculature to the trunk and increase vascular activity in the peripheral musculature.<br /> <br /> The adrenal glands are supplied by several branches of the great vessels in the abdominal cavity. The secreted catecholamines in the medulla are directly able to pass to the blood stream this way.<br /> <br /> These adrenal glands and their contents are retroperitoneal in the adult and varied in shape, with the left often being semilunar and right being pyramidal. Nervous supply of the adrenal glands is achieved by contributions from the splanchnic nerves of the celiac plexus.<br /> <br /> <br /> ====Role of the Adrenal Medulla====<br /> <br /> Understanding the biochemistry of catecholamines is necessary to see how the adrenal medulla is designed in the stages of embryology and how it is suited for life in the neonate and adult. <br /> <br /> The epinephrine and norepinephrine in the neonate and adult work by primarily changing the osmoregulatory state of vasculature in organs. With the exclusion of their neuromodulatory and neurotransmitter functions, epinephrine and norepinephrine are mainly tasked with the control of sympathetic and parasympathetic supplies. <br /> <br /> Norepinephrine is a constrictor of peripheral vasculature by antagonising the action of surface receptors expressed on the endothelium of blood vessels, specifically Alpha-1 and Alpha-2 receptors, such that vascular resistance increases. <br /> <br /> Epinephrine is both a vasoconstrictor and vasodilator, depending on what receptors it attaches to. As a non-selective adrenergic agonist, it acts on Alpha-1, Alpha-2, Beta-1, Beta-2 and Beta-3 receptors that are found throughout the body's tissues, yielding many different physiological responses.<br /> <br /> <br /> [[File:Dd.jpg|500px|thumb|right|Adult Adrenal Glands in situ]] <br /> ----<br /> <br /> ===Molecular mechanisms/factors/genes===<br /> ----<br /> <br /> ====Genes and Transcription Factors Involved with the Adrenal Medulla's Development====<br /> <br /> Members of the SOX (SRY-Box) gene family have multiple key contributors to Neural Crest in the Adrenal Medulla.<br /> <br /> Mouse models have demonstrated that SOX-10 knock-outs (mice whose DNA has been engineered to not express SOX-10) do not have an adrenal medulla. There has also been suggestion that SOX-8,9 and 10 are all strongly related to the migratory patterning of neural crest cells to the developing adrenal glands.<br /> <br /> The TH gene (for Tyrosine Hydroxylase) encodes the aforementioned enzyme in the adrenal medulla and central nervous system. Tyrosine Hydroxylase is crucial in biochemical pathways and cascades for the synthesis of catecholamines and other CNS neurotransmitters. The conversion from L-Tyrosine to L-DOPA is dependent upon the catalytic action of Tyrosine Hydroxylase. From there, L-DOPA can make Dopamine and eventually Epinephrine and Norepinephrine as well. <br /> <br /> [[File:Catecholamine_Synthesis.jpg|500px|thumb|right|Cascade of Catecholamine Synthesis]]<br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2291442/<br /> https://www.ncbi.nlm.nih.gov/pubmed/19396395<br /> <br /> ===Abnormalities/abnormal development===<br /> ----<br /> ===Animal models===<br /> ----<br /> Animal models are an integral part of research in embryology. In particular due to the moral concerns regarding the use of humans in scientific research. As a result different animals are used as substitutes to simulate the same environments and hope to achieve results that would also be able to represent humans as well. Prenatal adrenal gland development has been described in a number of scientific reports dating from the 1900s to studies in more recent years. These involved a variety of animal models such as ox, sheep, swine and most commonly mice. <br /> <br /> ====Chromaffin cells =(in rat models)====<br /> There has been extensive research conducted into the adrenal chromaffin cells and their embryological developments. As explained above nueral crest cells are pluripotent meaning they are able to differentiate into multiple different cells. The neural crest cells give rise to chromaffin cells of the adrenal medulla.<br /> <br /> To study the formation process of the adrenal medulla in the embryonic period, we visualized chromaffin cells of rat embryos at 13 to 17 days of gestation using anti-tyrosine hydroxylase (TH) antiserum, and created three-dimensional images from serial tissue sections. Between 13 and 15 days of gestation, TH-positive cells (chromaffin cells) migrated from a group of TH-positive cells present dorsal to the adrenal primordium via the medial cranial end of the adrenal primordium into the adrenal primordium. At or after 16 days of gestation, the adrenal capsule was formed except on the ventral aspect of the cranial end of the adrenal gland, from which TH-positive cells penetrated into the adrenal gland.(Pubmed: 15240937) <br /> <br /> Ahonen suggested that some neural crest cells continue migration from the chain ganglia to the lateral sides of aorta, where they form the perirenal ganglia and adrenal medulla, and finally to the ventral side of the aorta to form the preaortic sympathetic tissue. However, that report only showed the several transverse sections of the fetal trunk for the a demonstration of the migration route of neural crest cells. In this study, using three dimensional reconstructed images, we aimed to observe how TH-labeled chromaffin cells penetrate into the adrenal anlage to form the adrenal medulla and whether the migration route of TH - positive cells from the adrenal connects the preaortic sympathetic ganglia <br /> (M.Yamato, R. Yanai, K. Arishima, 2004) <br /> <br /> Prenatal adrenal gland development has been described in numerous published reports covering a wide variety of species, including the ox (Katznelson, 1966; Wrobel and Suss, 1999), sheep (Davies, 1950; Wintour et al., 1975; Upadhyay and Zamboni, 1982; Naaman‐Reperant and Durand, 1997; Grino, 2004), swine (Sokolov et al., 2006) and mouse (Waring, 1935; Ikeda et al., 1994; Sass, 1996; Nyska and Maronpot, 1999; Bland et al., 2003; Val et al., 2007). Adrenal gland development also has been extensively described for humans as well (Kolliker, 1879; Minot, 1892; Zuckerkandl, 1912; Wieman, 1920; Ikeda et al., 1981; Langlois et al., 2002; Hanley and Arit, 2006).<br /> <br /> https://www.sciencedirect.com/science/article/pii/S0925477302004550<br /> http://dev.biologists.org/content/develop/126/13/2935.full.pdf<br /> <br /> ===Current research (labs)===<br /> ----<br /> The findings presented until now have focused on the mechanisms controlling migration along the dorsolateral path. In comparison, our understanding of the mechanisms controlling NCC migration along the ventral path are complicated by the fact that this population comprises multiple precursors that form different derivatives in distinct regions of the embryo. For example, ventrally migrating NCCs either stop within the sclerotome in close association with the neural tube to form neurons and glia of the sensory nervous system (i.e. the dorsal root ganglia [DRG]), while other NCCs continue to migrate further ventrally to form the autonomic nervous system (i.e. sympathetic ganglia and chromaffin cells of the adrenal gland)<br /> <br /> Adrenomedullary chromaffin cells are catecholamine (CA)-producing cells originating from trunk neural crest (NC) via sympathoadrenal progenitors (SAPs). We generated NC and SAPs from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) in vitro via BMP2/FGF2 exposure, ascertained by qPCR and immunoexpression of SOX10, ASCL1, TFAP2α, and PHOX2B, and by fluorescence-activated cell sorting selection for p75NTR and GD2, and confirmed their trunk-like HOX gene expression. We showed that continuing BMP4 and curtailing FGF2 in vitro, augmented with corticosteroid mimetic, induced these cells to upregulate the chromaffin cell-specific marker PNMT and other CA synthesis and storage markers, and we demonstrated noradrenaline and adrenaline by Faglu and high-performance liquid chromatography. We showed these human cells' SAP-like property of migration and differentiation into cells expressing chromaffin cell markers by implanting them into avian embryos in vivo and in chorio-allantoic membrane grafts. These cells have the potential for investigating differentiation of human chromaffin cells and for modeling diseases involving this cell type.<br /> <br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768882/<br /> <br /> ===Glossary===<br /> ----<br /> ===Reference list===</div>

Z5091101 https://embryology.med.unsw.edu.au/embryology/index.php?title=2018_Group_Project_1&diff=356537 2018 Group Project 1 2018-10-09T07:47:53Z

<p>Z5091101: /* Embryonic origins */</p> <hr /> <div>=The Contribution of Neural Crest Cells to the Adrenal Medulla=<br /> ----<br /> {{2018ANAT2341ProjectHeader}}<br /> <br /> <br /> ===Introduction===<br /> [[User:Z5014972|Z5014972]] ([[User talk:Z5014972|talk]]) 12:47, 14 August 2018 (AEST)z5014972 <br /> good review article https://link.springer.com/article/10.1007%2Fs12022-009-9070-6<br /> ----<br /> <br /> <br /> The neural crest of an embryo differentiates and migrates to form various components of the body. One of these tissues is the medulla of the adrenal gland which is involved in the production of adrenalin and noradrenalin. This project will comprehensively outline the history of neural crest research, the embryonic developmental time course, tissue and organ structure, molecular mechanisms, abnormalities, animal models and current research.<br /> <br /> ===History===<br /> ----<br /> '''Describing the neural crest'''<br /> [[File:Wilhelm_His_History_Wilhelm.jpeg|left|230px|thumb|Wilhelm His]]<br /> The "neural crest" is a structure in the embryo and is the junction between the neural and epidermal ectoderm. It is exclusive to vertebrates and forms a range of structures{{#pmid:22230617|PMID22230617}}. The neural crest contributes a large number of cells of varying structure and function that directly or indirectly contribute to the development of tissues and organs within the body {{#pmid:19179766|PMID19179766}}. In 1868, the neural crest cells were first identified in a chick embryo as a collection of cells known as "Zwischenstrang" by Professor Wilhelm His {{#pmid:22820859|PMID22820859}}. Wilhelm His was among the first to provide an explanation for the mechanics governing the developing embryo as well as the physiology and the organs that the differing germinal regions would eventually give rise to. In 1878, the term neural ridge was used to describe this collection of cells but the term neural crest was later coined by Arthur Milnes Marshall in 1879 in a paper he worked on disseminating the knowledge from his research on the development of cranial nerves in chicken embryos. {{#pmid:19179766|PMID19179766}}.<br /> [[File:NC Location.jpg|left|450px|thumb|The neural crest]]<br /> <br /> '''1890s-1950s'''<br /> The neural crest is the point of origin for spinal/cranial ganglia and neurons. This theory received little criticism and was not contested much by other researchers prior to the 1890s. This is owing to the fact that the neural crest is quite closely related to the neural tube and thus this relationship makes sense. This discovery was made by His and Marshall, however, they found this out independently of one another.In the 1890s, Julia Platt, claimed that odontoblasts as well as the cartilages forming the facial and pharyngeal arch skeletons came from the ectoderm. This created much debate and was contested by many{{#pmid:22820859|PMID22820859}}. <br /> <br /> This is because this theory completely contradicted the germ-layer theory, whereby skeletal tissues originate at the mesoderm and not the ectoderm. The controversies this finding created brought about a slowing down of research, as demonstrated by a gap of almost 40 years between the theory that skeletal tissues originating from the neural crest. Today, it is known that the neural crest does indeed play a role in the development of the skeleton in vertebrates, particularly, the cranial neural crest. Although these studies were occurring, the focus was still primarily on researching pigment cells and ganglia of the spine up until the 1950s, when Sven Hörstadius' major work on the neural crest was published, titled "The Neural Crest: Its properties and derivatives in the light of experimental research". This work focused on experimental data tracing the development of the cartilaginous skeleton derived from the neural crest {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1960s - 1970s'''<br /> In the 1960s, the migration patterns of neural crest cells were studied in avian embryos (birds). This was a shift from studying the embryos of amphibians. This was inspired by studies conducted in the 1960s on neural crest cells migrating from the brain and spinal cord, known as trunk and cranial neural crest cells {{#pmid:19179766|PMID19179766}}. The cranial neural crest eventually becomes the bones, cartilage and connective tissues forming the foundation of the face, ears and teeth. The trunk neural crest cells can either become melanocytes or can migrate into sclerotomes which are later contributors to the cartilage of the spine and the dorsal root ganglia {{#pmid:22820859|PMID22820859}}. The cells in the trunk neural crest that migrate vertically become the sympathetic ganglia, the nerves proximal to the aorta and the adrenal medulla <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. In the 1970s many detailed maps signifying the pathways of many of the neural crest cells appeared as well as an understanding that the environment in which the neural crest cells are found plays a major role in their final development as well as the occurrences of abnormalities in the fetus {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1980s - 21st century'''<br /> [[File:Regions_of_NC_Cells.jpg|left|Neural crest regions|thumb]]<br /> From the 1980s-1990s, the causative agent of organ transformation from one to another (homeotic patterning), as well as the Hox genes which regulate the axis of most symmetrical animal embryos were founded and studied. The neural crest, which previously was divided into the cranial and trunk regions, was now further divided into the vagal and sacral neural crest, the cardiac neural crest and the cephalic neural crest {{#pmid:19179766|PMID19179766}}. The vagal & sacral neural crest gives rise to the parasympathetic ganglia found in the gut. Without these ganglia, peristalsis, is not possible <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. The cardiac neural crest contributes to the valves, septa and major blood vessels of the heart, as well as connective tissues and cartilage{{#pmid:19179766|PMID19179766}}. This is important for the structure of the heart as well as its overall function, enabling it to move blood around the body efficiently as well as keep pulmonary and aortic circulation separated <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> <br /> <br /> Today, knowledge of the neural crest cells, their migration patterns, modes of differentiation, derivatives and apoptosis (cell death) are being studied extensively. This is being done on a comparative basis between different organisms, to add further evidence for evolution {{#pmid:19179766|PMID19179766}}. The neural crest is definitely forging a "crest" between the fields of developmental and evolutionary biology, as it is a structure '''shared exclusively by all vertebrates'''. Invertebrates do not derive their specialised cells from the neural crest as they do not have one, rather, they derive these from the endomesoderm {{#pmid:22230617|PMID22230617}}.<br /> <br /> '''Future directions'''<br /> <br /> Since its discovery by His, the neural crest field has made great progress, from studies performed on the structure, to analysis of the molecules and whether certain aspects of the neural crest are specific to a single species of organism, or to all vertebrates collectively. Future work on the cranial neural crest needs to be done as well as identifying and categorising the networks responsible for the proliferation and death of cells, as well as how the cells move and migrate, as well as the gene regulatory networks (GRNs) that regulate the synthesis of proteins. Advances in technology will undeniable lead us to more answers on the subject {{#pmid:22230617|PMID22230617}}.<br /> <br /> ===Embryonic origins===<br /> ----<br /> https://www.ncbi.nlm.nih.gov/books/NBK10065/<br /> <br /> The adrenal gland is made up of the adrenal cortex and adrenal medulla, which both have different embryonic origins. The adrenal medulla arises from the neural crest tissue, found near the level of the coeliac plexus & sympathetic ganglion {{#pmid:16124976|PMID16124976}}. Specifically, this neural crest tissue comes from the trunk neural crest cells (see above figure to determine the approximate location in an embryo) <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> The trunk neural crest coordinates the development of the endocrine system, secretory cells, the peripheral nervous system and, to some degree, skeletal development, as well as innervation of the intestine {{#pmid: 28287247|PMID 28287247}}. The trunk neural cells arise caudally and follow three migratory pathways {{pmid:#20399766|PMID20399766}}:<br /> <br /> - A dorsolateral pathway<br /> - A ventrolateral pathway<br /> - A ventromedial pathway {{pmid:#20399766|PMID20399766}}<br /> <br /> ===Developmental time course===<br /> ----<br /> <br /> [[File:Adrenal_Medulla_Developmental_Timeline.jpg|right|thumb|500px]]<br /> <br /> The adrenal gland has two distinct sections, the cortex and the medulla, both with different embryonic origins. The cortex accounts for 90% of the adrenal glands and arises from intermediate mesoderm. The medulla only accounts for 10% of the adult adrenal glands, however it has neural crest embryonic origin. The medulla consists of chromaffinoblast cells which are migrant neuroblast cells from the neural crest, therefore the adrenal medulla is a component of the sympathetic nervous system.{{#pmid:21175739|PMID21175739}} Neural crest cells replicate in week 7 and begin to differentiate in week 8, the cells then migrate to the developing adrenal gland in week 9 of development.{{#pmid:25255746|PMID25255746}}{{#pmid:18279781|PMID18279781}} The neural crest cells infiltrate the cortex and the chromaffin cells are scattered islands in the cortex.{{#pmid:23354096|PMID23354096}} Throughout development the cells will become more compact in the centre of the gland, during this period of development the adrenal gland is growing rapidly. The gland is abnormally large until the second trimester and the medulla is much thicker prenatally.{{#pmid:18279781|PMID18279781}}{{#pmid:21175739|PMID21175739}}<br /> <br /> ===Developmental/adult function===<br /> ----<br /> ===Tissue and Organ structure===<br /> <br /> <br /> ====Normal Structure and Function of the Adrenal Medulla====<br /> <br /> The cells of the adrenal medulla are derived from the neural crest as opposed to the mesodermal origins of the cortex. The medulla contains secretory cells called chromaffin cells, due to the agents they produce when oxidised, such as chromate. These cells secrete epinephrine and norepinephrine in response to various substances such as acetylcholine.<br /> <br /> There are three types of cells in the adult adrenal medulla: <br /> 1) Epinephrine cells<br /> <br /> 2) Norepinephrine cells <br /> <br /> 3) Small granule-containing cells (SGCs)<br /> <br /> These cells also produce various other peptides such as substance P and neurotensin. The adrenal medulla also contains presynaptic sympathetic ganglion cells. {{#pmid:1694230|PMID1694230}}<br /> <br /> ====Related Anatomy====<br /> <br /> The tissue and organ structure of the adrenal medulla should be understood with regard to its specialised function within the sympathetic nervous system. <br /> <br /> The medullary region of the adrenal glands is tasked with the endocrine secretions of adrenaline and nor-adrenaline in response to environmental stressors that are signalled for by the sympathetic nervous system. That is, the secretion of fight-or-flight response hormones in order to restrict vasculature to the trunk and increase vascular activity in the peripheral musculature.<br /> <br /> The adrenal glands are supplied by several branches of the great vessels in the abdominal cavity. The secreted catecholamines in the medulla are directly able to pass to the blood stream this way.<br /> <br /> These adrenal glands and their contents are retroperitoneal in the adult and varied in shape, with the left often being semilunar and right being pyramidal. Nervous supply of the adrenal glands is achieved by contributions from the splanchnic nerves of the celiac plexus.<br /> <br /> <br /> ====Role of the Adrenal Medulla====<br /> <br /> Understanding the biochemistry of catecholamines is necessary to see how the adrenal medulla is designed in the stages of embryology and how it is suited for life in the neonate and adult. <br /> <br /> The epinephrine and norepinephrine in the neonate and adult work by primarily changing the osmoregulatory state of vasculature in organs. With the exclusion of their neuromodulatory and neurotransmitter functions, epinephrine and norepinephrine are mainly tasked with the control of sympathetic and parasympathetic supplies. <br /> <br /> Norepinephrine is a constrictor of peripheral vasculature by antagonising the action of surface receptors expressed on the endothelium of blood vessels, specifically Alpha-1 and Alpha-2 receptors, such that vascular resistance increases. <br /> <br /> Epinephrine is both a vasoconstrictor and vasodilator, depending on what receptors it attaches to. As a non-selective adrenergic agonist, it acts on Alpha-1, Alpha-2, Beta-1, Beta-2 and Beta-3 receptors that are found throughout the body's tissues, yielding many different physiological responses.<br /> <br /> <br /> [[File:Dd.jpg|500px|thumb|right|Adult Adrenal Glands in situ]] <br /> ----<br /> <br /> ===Molecular mechanisms/factors/genes===<br /> ----<br /> <br /> ====Genes and Transcription Factors Involved with the Adrenal Medulla's Development====<br /> <br /> Members of the SOX (SRY-Box) gene family have multiple key contributors to Neural Crest in the Adrenal Medulla.<br /> <br /> Mouse models have demonstrated that SOX-10 knock-outs (mice whose DNA has been engineered to not express SOX-10) do not have an adrenal medulla. There has also been suggestion that SOX-8,9 and 10 are all strongly related to the migratory patterning of neural crest cells to the developing adrenal glands.<br /> <br /> The TH gene (for Tyrosine Hydroxylase) encodes the aforementioned enzyme in the adrenal medulla and central nervous system. Tyrosine Hydroxylase is crucial in biochemical pathways and cascades for the synthesis of catecholamines and other CNS neurotransmitters. The conversion from L-Tyrosine to L-DOPA is dependent upon the catalytic action of Tyrosine Hydroxylase. From there, L-DOPA can make Dopamine and eventually Epinephrine and Norepinephrine as well. <br /> <br /> [[File:Catecholamine_Synthesis.jpg|500px|thumb|right|Cascade of Catecholamine Synthesis]]<br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2291442/<br /> https://www.ncbi.nlm.nih.gov/pubmed/19396395<br /> <br /> ===Abnormalities/abnormal development===<br /> ----<br /> ===Animal models===<br /> ----<br /> Animal models are an integral part of research in embryology. In particular due to the moral concerns regarding the use of humans in scientific research. As a result different animals are used as substitutes to simulate the same environments and hope to achieve results that would also be able to represent humans as well. Prenatal adrenal gland development has been described in a number of scientific reports dating from the 1900s to studies in more recent years. These involved a variety of animal models such as ox, sheep, swine and most commonly mice. <br /> <br /> ====Chromaffin cells =(in rat models)====<br /> There has been extensive research conducted into the adrenal chromaffin cells and their embryological developments. As explained above nueral crest cells are pluripotent meaning they are able to differentiate into multiple different cells. The neural crest cells give rise to chromaffin cells of the adrenal medulla.<br /> <br /> To study the formation process of the adrenal medulla in the embryonic period, we visualized chromaffin cells of rat embryos at 13 to 17 days of gestation using anti-tyrosine hydroxylase (TH) antiserum, and created three-dimensional images from serial tissue sections. Between 13 and 15 days of gestation, TH-positive cells (chromaffin cells) migrated from a group of TH-positive cells present dorsal to the adrenal primordium via the medial cranial end of the adrenal primordium into the adrenal primordium. At or after 16 days of gestation, the adrenal capsule was formed except on the ventral aspect of the cranial end of the adrenal gland, from which TH-positive cells penetrated into the adrenal gland.(Pubmed: 15240937) <br /> <br /> Ahonen suggested that some neural crest cells continue migration from the chain ganglia to the lateral sides of aorta, where they form the perirenal ganglia and adrenal medulla, and finally to the ventral side of the aorta to form the preaortic sympathetic tissue. However, that report only showed the several transverse sections of the fetal trunk for the a demonstration of the migration route of neural crest cells. In this study, using three dimensional reconstructed images, we aimed to observe how TH-labeled chromaffin cells penetrate into the adrenal anlage to form the adrenal medulla and whether the migration route of TH - positive cells from the adrenal connects the preaortic sympathetic ganglia <br /> (M.Yamato, R. Yanai, K. Arishima, 2004) <br /> <br /> Prenatal adrenal gland development has been described in numerous published reports covering a wide variety of species, including the ox (Katznelson, 1966; Wrobel and Suss, 1999), sheep (Davies, 1950; Wintour et al., 1975; Upadhyay and Zamboni, 1982; Naaman‐Reperant and Durand, 1997; Grino, 2004), swine (Sokolov et al., 2006) and mouse (Waring, 1935; Ikeda et al., 1994; Sass, 1996; Nyska and Maronpot, 1999; Bland et al., 2003; Val et al., 2007). Adrenal gland development also has been extensively described for humans as well (Kolliker, 1879; Minot, 1892; Zuckerkandl, 1912; Wieman, 1920; Ikeda et al., 1981; Langlois et al., 2002; Hanley and Arit, 2006).<br /> <br /> https://www.sciencedirect.com/science/article/pii/S0925477302004550<br /> http://dev.biologists.org/content/develop/126/13/2935.full.pdf<br /> <br /> ===Current research (labs)===<br /> ----<br /> The findings presented until now have focused on the mechanisms controlling migration along the dorsolateral path. In comparison, our understanding of the mechanisms controlling NCC migration along the ventral path are complicated by the fact that this population comprises multiple precursors that form different derivatives in distinct regions of the embryo. For example, ventrally migrating NCCs either stop within the sclerotome in close association with the neural tube to form neurons and glia of the sensory nervous system (i.e. the dorsal root ganglia [DRG]), while other NCCs continue to migrate further ventrally to form the autonomic nervous system (i.e. sympathetic ganglia and chromaffin cells of the adrenal gland)<br /> <br /> Adrenomedullary chromaffin cells are catecholamine (CA)-producing cells originating from trunk neural crest (NC) via sympathoadrenal progenitors (SAPs). We generated NC and SAPs from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) in vitro via BMP2/FGF2 exposure, ascertained by qPCR and immunoexpression of SOX10, ASCL1, TFAP2α, and PHOX2B, and by fluorescence-activated cell sorting selection for p75NTR and GD2, and confirmed their trunk-like HOX gene expression. We showed that continuing BMP4 and curtailing FGF2 in vitro, augmented with corticosteroid mimetic, induced these cells to upregulate the chromaffin cell-specific marker PNMT and other CA synthesis and storage markers, and we demonstrated noradrenaline and adrenaline by Faglu and high-performance liquid chromatography. We showed these human cells' SAP-like property of migration and differentiation into cells expressing chromaffin cell markers by implanting them into avian embryos in vivo and in chorio-allantoic membrane grafts. These cells have the potential for investigating differentiation of human chromaffin cells and for modeling diseases involving this cell type.<br /> <br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768882/<br /> <br /> ===Glossary===<br /> ----<br /> ===Reference list===</div>

Z5091101 https://embryology.med.unsw.edu.au/embryology/index.php?title=2018_Group_Project_1&diff=356535 2018 Group Project 1 2018-10-09T07:47:12Z

<p>Z5091101: /* Embryonic origins */</p> <hr /> <div>=The Contribution of Neural Crest Cells to the Adrenal Medulla=<br /> ----<br /> {{2018ANAT2341ProjectHeader}}<br /> <br /> <br /> ===Introduction===<br /> [[User:Z5014972|Z5014972]] ([[User talk:Z5014972|talk]]) 12:47, 14 August 2018 (AEST)z5014972 <br /> good review article https://link.springer.com/article/10.1007%2Fs12022-009-9070-6<br /> ----<br /> <br /> <br /> The neural crest of an embryo differentiates and migrates to form various components of the body. One of these tissues is the medulla of the adrenal gland which is involved in the production of adrenalin and noradrenalin. This project will comprehensively outline the history of neural crest research, the embryonic developmental time course, tissue and organ structure, molecular mechanisms, abnormalities, animal models and current research.<br /> <br /> ===History===<br /> ----<br /> '''Describing the neural crest'''<br /> [[File:Wilhelm_His_History_Wilhelm.jpeg|left|230px|thumb|Wilhelm His]]<br /> The "neural crest" is a structure in the embryo and is the junction between the neural and epidermal ectoderm. It is exclusive to vertebrates and forms a range of structures{{#pmid:22230617|PMID22230617}}. The neural crest contributes a large number of cells of varying structure and function that directly or indirectly contribute to the development of tissues and organs within the body {{#pmid:19179766|PMID19179766}}. In 1868, the neural crest cells were first identified in a chick embryo as a collection of cells known as "Zwischenstrang" by Professor Wilhelm His {{#pmid:22820859|PMID22820859}}. Wilhelm His was among the first to provide an explanation for the mechanics governing the developing embryo as well as the physiology and the organs that the differing germinal regions would eventually give rise to. In 1878, the term neural ridge was used to describe this collection of cells but the term neural crest was later coined by Arthur Milnes Marshall in 1879 in a paper he worked on disseminating the knowledge from his research on the development of cranial nerves in chicken embryos. {{#pmid:19179766|PMID19179766}}.<br /> [[File:NC Location.jpg|left|450px|thumb|The neural crest]]<br /> <br /> '''1890s-1950s'''<br /> The neural crest is the point of origin for spinal/cranial ganglia and neurons. This theory received little criticism and was not contested much by other researchers prior to the 1890s. This is owing to the fact that the neural crest is quite closely related to the neural tube and thus this relationship makes sense. This discovery was made by His and Marshall, however, they found this out independently of one another.In the 1890s, Julia Platt, claimed that odontoblasts as well as the cartilages forming the facial and pharyngeal arch skeletons came from the ectoderm. This created much debate and was contested by many{{#pmid:22820859|PMID22820859}}. <br /> <br /> This is because this theory completely contradicted the germ-layer theory, whereby skeletal tissues originate at the mesoderm and not the ectoderm. The controversies this finding created brought about a slowing down of research, as demonstrated by a gap of almost 40 years between the theory that skeletal tissues originating from the neural crest. Today, it is known that the neural crest does indeed play a role in the development of the skeleton in vertebrates, particularly, the cranial neural crest. Although these studies were occurring, the focus was still primarily on researching pigment cells and ganglia of the spine up until the 1950s, when Sven Hörstadius' major work on the neural crest was published, titled "The Neural Crest: Its properties and derivatives in the light of experimental research". This work focused on experimental data tracing the development of the cartilaginous skeleton derived from the neural crest {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1960s - 1970s'''<br /> In the 1960s, the migration patterns of neural crest cells were studied in avian embryos (birds). This was a shift from studying the embryos of amphibians. This was inspired by studies conducted in the 1960s on neural crest cells migrating from the brain and spinal cord, known as trunk and cranial neural crest cells {{#pmid:19179766|PMID19179766}}. The cranial neural crest eventually becomes the bones, cartilage and connective tissues forming the foundation of the face, ears and teeth. The trunk neural crest cells can either become melanocytes or can migrate into sclerotomes which are later contributors to the cartilage of the spine and the dorsal root ganglia {{#pmid:22820859|PMID22820859}}. The cells in the trunk neural crest that migrate vertically become the sympathetic ganglia, the nerves proximal to the aorta and the adrenal medulla <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. In the 1970s many detailed maps signifying the pathways of many of the neural crest cells appeared as well as an understanding that the environment in which the neural crest cells are found plays a major role in their final development as well as the occurrences of abnormalities in the fetus {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1980s - 21st century'''<br /> [[File:Regions_of_NC_Cells.jpg|left|Neural crest regions|thumb]]<br /> From the 1980s-1990s, the causative agent of organ transformation from one to another (homeotic patterning), as well as the Hox genes which regulate the axis of most symmetrical animal embryos were founded and studied. The neural crest, which previously was divided into the cranial and trunk regions, was now further divided into the vagal and sacral neural crest, the cardiac neural crest and the cephalic neural crest {{#pmid:19179766|PMID19179766}}. The vagal & sacral neural crest gives rise to the parasympathetic ganglia found in the gut. Without these ganglia, peristalsis, is not possible <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. The cardiac neural crest contributes to the valves, septa and major blood vessels of the heart, as well as connective tissues and cartilage{{#pmid:19179766|PMID19179766}}. This is important for the structure of the heart as well as its overall function, enabling it to move blood around the body efficiently as well as keep pulmonary and aortic circulation separated <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> <br /> <br /> Today, knowledge of the neural crest cells, their migration patterns, modes of differentiation, derivatives and apoptosis (cell death) are being studied extensively. This is being done on a comparative basis between different organisms, to add further evidence for evolution {{#pmid:19179766|PMID19179766}}. The neural crest is definitely forging a "crest" between the fields of developmental and evolutionary biology, as it is a structure '''shared exclusively by all vertebrates'''. Invertebrates do not derive their specialised cells from the neural crest as they do not have one, rather, they derive these from the endomesoderm {{#pmid:22230617|PMID22230617}}.<br /> <br /> '''Future directions'''<br /> <br /> Since its discovery by His, the neural crest field has made great progress, from studies performed on the structure, to analysis of the molecules and whether certain aspects of the neural crest are specific to a single species of organism, or to all vertebrates collectively. Future work on the cranial neural crest needs to be done as well as identifying and categorising the networks responsible for the proliferation and death of cells, as well as how the cells move and migrate, as well as the gene regulatory networks (GRNs) that regulate the synthesis of proteins. Advances in technology will undeniable lead us to more answers on the subject {{#pmid:22230617|PMID22230617}}.<br /> <br /> ===Embryonic origins===<br /> ----<br /> https://www.ncbi.nlm.nih.gov/books/NBK10065/<br /> <br /> The adrenal gland is made up of the adrenal cortex and adrenal medulla, which both have different embryonic origins. The adrenal medulla arises from the neural crest tissue, found near the level of the coeliac plexus & sympathetic ganglion {{#pmid:16124976|PMID16124976}}. Specifically, this neural crest tissue comes from the trunk neural crest cells (see above figure to determine the approximate location in an embryo) <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> The trunk neural crest coordinates the development of the endocrine system, secretory cells, the peripheral nervous system and, to some degree, skeletal development, as well as innervation of the intestine {{#pmid: 28287247|PMID 28287247}}. The trunk neural cells arise caudally and follow three migratory pathways {{pmid#20399766|PMID20399766}}:<br /> <br /> - A dorsolateral pathway<br /> - A ventrolateral pathway<br /> - A ventromedial pathway {{pmid#20399766|PMID20399766}}<br /> <br /> ===Developmental time course===<br /> ----<br /> <br /> [[File:Adrenal_Medulla_Developmental_Timeline.jpg|right|thumb|500px]]<br /> <br /> The adrenal gland has two distinct sections, the cortex and the medulla, both with different embryonic origins. The cortex accounts for 90% of the adrenal glands and arises from intermediate mesoderm. The medulla only accounts for 10% of the adult adrenal glands, however it has neural crest embryonic origin. The medulla consists of chromaffinoblast cells which are migrant neuroblast cells from the neural crest, therefore the adrenal medulla is a component of the sympathetic nervous system.{{#pmid:21175739|PMID21175739}} Neural crest cells replicate in week 7 and begin to differentiate in week 8, the cells then migrate to the developing adrenal gland in week 9 of development.{{#pmid:25255746|PMID25255746}}{{#pmid:18279781|PMID18279781}} The neural crest cells infiltrate the cortex and the chromaffin cells are scattered islands in the cortex.{{#pmid:23354096|PMID23354096}} Throughout development the cells will become more compact in the centre of the gland, during this period of development the adrenal gland is growing rapidly. The gland is abnormally large until the second trimester and the medulla is much thicker prenatally.{{#pmid:18279781|PMID18279781}}{{#pmid:21175739|PMID21175739}}<br /> <br /> ===Developmental/adult function===<br /> ----<br /> ===Tissue and Organ structure===<br /> <br /> <br /> ====Normal Structure and Function of the Adrenal Medulla====<br /> <br /> The cells of the adrenal medulla are derived from the neural crest as opposed to the mesodermal origins of the cortex. The medulla contains secretory cells called chromaffin cells, due to the agents they produce when oxidised, such as chromate. These cells secrete epinephrine and norepinephrine in response to various substances such as acetylcholine.<br /> <br /> There are three types of cells in the adult adrenal medulla: <br /> 1) Epinephrine cells<br /> <br /> 2) Norepinephrine cells <br /> <br /> 3) Small granule-containing cells (SGCs)<br /> <br /> These cells also produce various other peptides such as substance P and neurotensin. The adrenal medulla also contains presynaptic sympathetic ganglion cells. {{#pmid:1694230|PMID1694230}}<br /> <br /> ====Related Anatomy====<br /> <br /> The tissue and organ structure of the adrenal medulla should be understood with regard to its specialised function within the sympathetic nervous system. <br /> <br /> The medullary region of the adrenal glands is tasked with the endocrine secretions of adrenaline and nor-adrenaline in response to environmental stressors that are signalled for by the sympathetic nervous system. That is, the secretion of fight-or-flight response hormones in order to restrict vasculature to the trunk and increase vascular activity in the peripheral musculature.<br /> <br /> The adrenal glands are supplied by several branches of the great vessels in the abdominal cavity. The secreted catecholamines in the medulla are directly able to pass to the blood stream this way.<br /> <br /> These adrenal glands and their contents are retroperitoneal in the adult and varied in shape, with the left often being semilunar and right being pyramidal. Nervous supply of the adrenal glands is achieved by contributions from the splanchnic nerves of the celiac plexus.<br /> <br /> <br /> ====Role of the Adrenal Medulla====<br /> <br /> Understanding the biochemistry of catecholamines is necessary to see how the adrenal medulla is designed in the stages of embryology and how it is suited for life in the neonate and adult. <br /> <br /> The epinephrine and norepinephrine in the neonate and adult work by primarily changing the osmoregulatory state of vasculature in organs. With the exclusion of their neuromodulatory and neurotransmitter functions, epinephrine and norepinephrine are mainly tasked with the control of sympathetic and parasympathetic supplies. <br /> <br /> Norepinephrine is a constrictor of peripheral vasculature by antagonising the action of surface receptors expressed on the endothelium of blood vessels, specifically Alpha-1 and Alpha-2 receptors, such that vascular resistance increases. <br /> <br /> Epinephrine is both a vasoconstrictor and vasodilator, depending on what receptors it attaches to. As a non-selective adrenergic agonist, it acts on Alpha-1, Alpha-2, Beta-1, Beta-2 and Beta-3 receptors that are found throughout the body's tissues, yielding many different physiological responses.<br /> <br /> <br /> [[File:Dd.jpg|500px|thumb|right|Adult Adrenal Glands in situ]] <br /> ----<br /> <br /> ===Molecular mechanisms/factors/genes===<br /> ----<br /> <br /> ====Genes and Transcription Factors Involved with the Adrenal Medulla's Development====<br /> <br /> Members of the SOX (SRY-Box) gene family have multiple key contributors to Neural Crest in the Adrenal Medulla.<br /> <br /> Mouse models have demonstrated that SOX-10 knock-outs (mice whose DNA has been engineered to not express SOX-10) do not have an adrenal medulla. There has also been suggestion that SOX-8,9 and 10 are all strongly related to the migratory patterning of neural crest cells to the developing adrenal glands.<br /> <br /> The TH gene (for Tyrosine Hydroxylase) encodes the aforementioned enzyme in the adrenal medulla and central nervous system. Tyrosine Hydroxylase is crucial in biochemical pathways and cascades for the synthesis of catecholamines and other CNS neurotransmitters. The conversion from L-Tyrosine to L-DOPA is dependent upon the catalytic action of Tyrosine Hydroxylase. From there, L-DOPA can make Dopamine and eventually Epinephrine and Norepinephrine as well. <br /> <br /> [[File:Catecholamine_Synthesis.jpg|500px|thumb|right|Cascade of Catecholamine Synthesis]]<br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2291442/<br /> https://www.ncbi.nlm.nih.gov/pubmed/19396395<br /> <br /> ===Abnormalities/abnormal development===<br /> ----<br /> ===Animal models===<br /> ----<br /> Animal models are an integral part of research in embryology. In particular due to the moral concerns regarding the use of humans in scientific research. As a result different animals are used as substitutes to simulate the same environments and hope to achieve results that would also be able to represent humans as well. Prenatal adrenal gland development has been described in a number of scientific reports dating from the 1900s to studies in more recent years. These involved a variety of animal models such as ox, sheep, swine and most commonly mice. <br /> <br /> ====Chromaffin cells =(in rat models)====<br /> There has been extensive research conducted into the adrenal chromaffin cells and their embryological developments. As explained above nueral crest cells are pluripotent meaning they are able to differentiate into multiple different cells. The neural crest cells give rise to chromaffin cells of the adrenal medulla.<br /> <br /> To study the formation process of the adrenal medulla in the embryonic period, we visualized chromaffin cells of rat embryos at 13 to 17 days of gestation using anti-tyrosine hydroxylase (TH) antiserum, and created three-dimensional images from serial tissue sections. Between 13 and 15 days of gestation, TH-positive cells (chromaffin cells) migrated from a group of TH-positive cells present dorsal to the adrenal primordium via the medial cranial end of the adrenal primordium into the adrenal primordium. At or after 16 days of gestation, the adrenal capsule was formed except on the ventral aspect of the cranial end of the adrenal gland, from which TH-positive cells penetrated into the adrenal gland.(Pubmed: 15240937) <br /> <br /> Ahonen suggested that some neural crest cells continue migration from the chain ganglia to the lateral sides of aorta, where they form the perirenal ganglia and adrenal medulla, and finally to the ventral side of the aorta to form the preaortic sympathetic tissue. However, that report only showed the several transverse sections of the fetal trunk for the a demonstration of the migration route of neural crest cells. In this study, using three dimensional reconstructed images, we aimed to observe how TH-labeled chromaffin cells penetrate into the adrenal anlage to form the adrenal medulla and whether the migration route of TH - positive cells from the adrenal connects the preaortic sympathetic ganglia <br /> (M.Yamato, R. Yanai, K. Arishima, 2004) <br /> <br /> Prenatal adrenal gland development has been described in numerous published reports covering a wide variety of species, including the ox (Katznelson, 1966; Wrobel and Suss, 1999), sheep (Davies, 1950; Wintour et al., 1975; Upadhyay and Zamboni, 1982; Naaman‐Reperant and Durand, 1997; Grino, 2004), swine (Sokolov et al., 2006) and mouse (Waring, 1935; Ikeda et al., 1994; Sass, 1996; Nyska and Maronpot, 1999; Bland et al., 2003; Val et al., 2007). Adrenal gland development also has been extensively described for humans as well (Kolliker, 1879; Minot, 1892; Zuckerkandl, 1912; Wieman, 1920; Ikeda et al., 1981; Langlois et al., 2002; Hanley and Arit, 2006).<br /> <br /> https://www.sciencedirect.com/science/article/pii/S0925477302004550<br /> http://dev.biologists.org/content/develop/126/13/2935.full.pdf<br /> <br /> ===Current research (labs)===<br /> ----<br /> The findings presented until now have focused on the mechanisms controlling migration along the dorsolateral path. In comparison, our understanding of the mechanisms controlling NCC migration along the ventral path are complicated by the fact that this population comprises multiple precursors that form different derivatives in distinct regions of the embryo. For example, ventrally migrating NCCs either stop within the sclerotome in close association with the neural tube to form neurons and glia of the sensory nervous system (i.e. the dorsal root ganglia [DRG]), while other NCCs continue to migrate further ventrally to form the autonomic nervous system (i.e. sympathetic ganglia and chromaffin cells of the adrenal gland)<br /> <br /> Adrenomedullary chromaffin cells are catecholamine (CA)-producing cells originating from trunk neural crest (NC) via sympathoadrenal progenitors (SAPs). We generated NC and SAPs from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) in vitro via BMP2/FGF2 exposure, ascertained by qPCR and immunoexpression of SOX10, ASCL1, TFAP2α, and PHOX2B, and by fluorescence-activated cell sorting selection for p75NTR and GD2, and confirmed their trunk-like HOX gene expression. We showed that continuing BMP4 and curtailing FGF2 in vitro, augmented with corticosteroid mimetic, induced these cells to upregulate the chromaffin cell-specific marker PNMT and other CA synthesis and storage markers, and we demonstrated noradrenaline and adrenaline by Faglu and high-performance liquid chromatography. We showed these human cells' SAP-like property of migration and differentiation into cells expressing chromaffin cell markers by implanting them into avian embryos in vivo and in chorio-allantoic membrane grafts. These cells have the potential for investigating differentiation of human chromaffin cells and for modeling diseases involving this cell type.<br /> <br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768882/<br /> <br /> ===Glossary===<br /> ----<br /> ===Reference list===</div>

Z5091101 https://embryology.med.unsw.edu.au/embryology/index.php?title=2018_Group_Project_1&diff=356533 2018 Group Project 1 2018-10-09T06:56:04Z

<p>Z5091101: /* Embryonic origins */</p> <hr /> <div>=The Contribution of Neural Crest Cells to the Adrenal Medulla=<br /> ----<br /> {{2018ANAT2341ProjectHeader}}<br /> <br /> <br /> ===Introduction===<br /> [[User:Z5014972|Z5014972]] ([[User talk:Z5014972|talk]]) 12:47, 14 August 2018 (AEST)z5014972 <br /> good review article https://link.springer.com/article/10.1007%2Fs12022-009-9070-6<br /> ----<br /> <br /> <br /> The neural crest of an embryo differentiates and migrates to form various components of the body. One of these tissues is the medulla of the adrenal gland which is involved in the production of adrenalin and noradrenalin. This project will comprehensively outline the history of neural crest research, the embryonic developmental time course, tissue and organ structure, molecular mechanisms, abnormalities, animal models and current research.<br /> <br /> ===History===<br /> ----<br /> '''Describing the neural crest'''<br /> [[File:Wilhelm_His_History_Wilhelm.jpeg|left|230px|thumb|Wilhelm His]]<br /> The "neural crest" is a structure in the embryo and is the junction between the neural and epidermal ectoderm. It is exclusive to vertebrates and forms a range of structures{{#pmid:22230617|PMID22230617}}. The neural crest contributes a large number of cells of varying structure and function that directly or indirectly contribute to the development of tissues and organs within the body {{#pmid:19179766|PMID19179766}}. In 1868, the neural crest cells were first identified in a chick embryo as a collection of cells known as "Zwischenstrang" by Professor Wilhelm His {{#pmid:22820859|PMID22820859}}. Wilhelm His was among the first to provide an explanation for the mechanics governing the developing embryo as well as the physiology and the organs that the differing germinal regions would eventually give rise to. In 1878, the term neural ridge was used to describe this collection of cells but the term neural crest was later coined by Arthur Milnes Marshall in 1879 in a paper he worked on disseminating the knowledge from his research on the development of cranial nerves in chicken embryos. {{#pmid:19179766|PMID19179766}}.<br /> [[File:NC Location.jpg|left|450px|thumb|The neural crest]]<br /> <br /> '''1890s-1950s'''<br /> The neural crest is the point of origin for spinal/cranial ganglia and neurons. This theory received little criticism and was not contested much by other researchers prior to the 1890s. This is owing to the fact that the neural crest is quite closely related to the neural tube and thus this relationship makes sense. This discovery was made by His and Marshall, however, they found this out independently of one another.In the 1890s, Julia Platt, claimed that odontoblasts as well as the cartilages forming the facial and pharyngeal arch skeletons came from the ectoderm. This created much debate and was contested by many{{#pmid:22820859|PMID22820859}}. <br /> <br /> This is because this theory completely contradicted the germ-layer theory, whereby skeletal tissues originate at the mesoderm and not the ectoderm. The controversies this finding created brought about a slowing down of research, as demonstrated by a gap of almost 40 years between the theory that skeletal tissues originating from the neural crest. Today, it is known that the neural crest does indeed play a role in the development of the skeleton in vertebrates, particularly, the cranial neural crest. Although these studies were occurring, the focus was still primarily on researching pigment cells and ganglia of the spine up until the 1950s, when Sven Hörstadius' major work on the neural crest was published, titled "The Neural Crest: Its properties and derivatives in the light of experimental research". This work focused on experimental data tracing the development of the cartilaginous skeleton derived from the neural crest {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1960s - 1970s'''<br /> In the 1960s, the migration patterns of neural crest cells were studied in avian embryos (birds). This was a shift from studying the embryos of amphibians. This was inspired by studies conducted in the 1960s on neural crest cells migrating from the brain and spinal cord, known as trunk and cranial neural crest cells {{#pmid:19179766|PMID19179766}}. The cranial neural crest eventually becomes the bones, cartilage and connective tissues forming the foundation of the face, ears and teeth. The trunk neural crest cells can either become melanocytes or can migrate into sclerotomes which are later contributors to the cartilage of the spine and the dorsal root ganglia {{#pmid:22820859|PMID22820859}}. The cells in the trunk neural crest that migrate vertically become the sympathetic ganglia, the nerves proximal to the aorta and the adrenal medulla <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. In the 1970s many detailed maps signifying the pathways of many of the neural crest cells appeared as well as an understanding that the environment in which the neural crest cells are found plays a major role in their final development as well as the occurrences of abnormalities in the fetus {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1980s - 21st century'''<br /> [[File:Regions_of_NC_Cells.jpg|left|Neural crest regions|thumb]]<br /> From the 1980s-1990s, the causative agent of organ transformation from one to another (homeotic patterning), as well as the Hox genes which regulate the axis of most symmetrical animal embryos were founded and studied. The neural crest, which previously was divided into the cranial and trunk regions, was now further divided into the vagal and sacral neural crest, the cardiac neural crest and the cephalic neural crest {{#pmid:19179766|PMID19179766}}. The vagal & sacral neural crest gives rise to the parasympathetic ganglia found in the gut. Without these ganglia, peristalsis, is not possible <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. The cardiac neural crest contributes to the valves, septa and major blood vessels of the heart, as well as connective tissues and cartilage{{#pmid:19179766|PMID19179766}}. This is important for the structure of the heart as well as its overall function, enabling it to move blood around the body efficiently as well as keep pulmonary and aortic circulation separated <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> <br /> <br /> Today, knowledge of the neural crest cells, their migration patterns, modes of differentiation, derivatives and apoptosis (cell death) are being studied extensively. This is being done on a comparative basis between different organisms, to add further evidence for evolution {{#pmid:19179766|PMID19179766}}. The neural crest is definitely forging a "crest" between the fields of developmental and evolutionary biology, as it is a structure '''shared exclusively by all vertebrates'''. Invertebrates do not derive their specialised cells from the neural crest as they do not have one, rather, they derive these from the endomesoderm {{#pmid:22230617|PMID22230617}}.<br /> <br /> '''Future directions'''<br /> <br /> Since its discovery by His, the neural crest field has made great progress, from studies performed on the structure, to analysis of the molecules and whether certain aspects of the neural crest are specific to a single species of organism, or to all vertebrates collectively. Future work on the cranial neural crest needs to be done as well as identifying and categorising the networks responsible for the proliferation and death of cells, as well as how the cells move and migrate, as well as the gene regulatory networks (GRNs) that regulate the synthesis of proteins. Advances in technology will undeniable lead us to more answers on the subject {{#pmid:22230617|PMID22230617}}.<br /> <br /> ===Embryonic origins===<br /> ----<br /> https://www.ncbi.nlm.nih.gov/books/NBK10065/<br /> <br /> The adrenal gland is made up of the adrenal cortex and adrenal medulla, which both have different embryonic origins. The adrenal medulla arises from the neural crest tissue, found near the level of the coeliac plexus & sympathetic ganglion {{#pmid:16124976|PMID16124976}}.<br /> <br /> ===Developmental time course===<br /> ----<br /> <br /> [[File:Adrenal_Medulla_Developmental_Timeline.jpg|right|thumb|500px]]<br /> <br /> The adrenal gland has two distinct sections, the cortex and the medulla, both with different embryonic origins. The cortex accounts for 90% of the adrenal glands and arises from intermediate mesoderm. The medulla only accounts for 10% of the adult adrenal glands, however it has neural crest embryonic origin. The medulla consists of chromaffinoblast cells which are migrant neuroblast cells from the neural crest, therefore the adrenal medulla is a component of the sympathetic nervous system.{{#pmid:21175739|PMID21175739}} Neural crest cells replicate in week 7 and begin to differentiate in week 8, the cells then migrate to the developing adrenal gland in week 9 of development.{{#pmid:25255746|PMID25255746}}{{#pmid:18279781|PMID18279781}} The neural crest cells infiltrate the cortex and the chromaffin cells are scattered islands in the cortex.{{#pmid:23354096|PMID23354096}} Throughout development the cells will become more compact in the centre of the gland, during this period of development the adrenal gland is growing rapidly. The gland is abnormally large until the second trimester and the medulla is much thicker prenatally.{{#pmid:18279781|PMID18279781}}{{#pmid:21175739|PMID21175739}}<br /> <br /> ===Developmental/adult function===<br /> ----<br /> ===Tissue and Organ structure===<br /> <br /> <br /> ====Normal Structure and Function of the Adrenal Medulla====<br /> <br /> The cells of the adrenal medulla are derived from the neural crest as opposed to the mesodermal origins of the cortex. The medulla contains secretory cells called chromaffin cells, due to the agents they produce when oxidised, such as chromate. These cells secrete epinephrine and norepinephrine in response to various substances such as acetylcholine.<br /> <br /> There are three types of cells in the adult adrenal medulla: <br /> 1) Epinephrine cells<br /> <br /> 2) Norepinephrine cells <br /> <br /> 3) Small granule-containing cells (SGCs)<br /> <br /> These cells also produce various other peptides such as substance P and neurotensin. The adrenal medulla also contains presynaptic sympathetic ganglion cells. {{#pmid:1694230|PMID1694230}}<br /> <br /> ====Related Anatomy====<br /> <br /> The tissue and organ structure of the adrenal medulla should be understood with regard to its specialised function within the sympathetic nervous system. <br /> <br /> The medullary region of the adrenal glands is tasked with the endocrine secretions of adrenaline and nor-adrenaline in response to environmental stressors that are signalled for by the sympathetic nervous system. That is, the secretion of fight-or-flight response hormones in order to restrict vasculature to the trunk and increase vascular activity in the peripheral musculature.<br /> <br /> The adrenal glands are supplied by several branches of the great vessels in the abdominal cavity. The secreted catecholamines in the medulla are directly able to pass to the blood stream this way.<br /> <br /> These adrenal glands and their contents are retroperitoneal in the adult and varied in shape, with the left often being semilunar and right being pyramidal. Nervous supply of the adrenal glands is achieved by contributions from the splanchnic nerves of the celiac plexus.<br /> <br /> <br /> ====Role of the Adrenal Medulla====<br /> <br /> Understanding the biochemistry of catecholamines is necessary to see how the adrenal medulla is designed in the stages of embryology and how it is suited for life in the neonate and adult. <br /> <br /> The epinephrine and norepinephrine in the neonate and adult work by primarily changing the osmoregulatory state of vasculature in organs. With the exclusion of their neuromodulatory and neurotransmitter functions, epinephrine and norepinephrine are mainly tasked with the control of sympathetic and parasympathetic supplies. <br /> <br /> Norepinephrine is a constrictor of peripheral vasculature by antagonising the action of surface receptors expressed on the endothelium of blood vessels, specifically Alpha-1 and Alpha-2 receptors, such that vascular resistance increases. <br /> <br /> Epinephrine is both a vasoconstrictor and vasodilator, depending on what receptors it attaches to. As a non-selective adrenergic agonist, it acts on Alpha-1, Alpha-2, Beta-1, Beta-2 and Beta-3 receptors that are found throughout the body's tissues, yielding many different physiological responses.<br /> <br /> <br /> [[File:Dd.jpg|500px|thumb|right|Adult Adrenal Glands in situ]] <br /> ----<br /> <br /> ===Molecular mechanisms/factors/genes===<br /> ----<br /> <br /> ====Genes and Transcription Factors Involved with the Adrenal Medulla's Development====<br /> <br /> Members of the SOX (SRY-Box) gene family have multiple key contributors to Neural Crest in the Adrenal Medulla.<br /> <br /> Mouse models have demonstrated that SOX-10 knock-outs (mice whose DNA has been engineered to not express SOX-10) do not have an adrenal medulla. There has also been suggestion that SOX-8,9 and 10 are all strongly related to the migratory patterning of neural crest cells to the developing adrenal glands.<br /> <br /> The TH gene (for Tyrosine Hydroxylase) encodes the aforementioned enzyme in the adrenal medulla and central nervous system. Tyrosine Hydroxylase is crucial in biochemical pathways and cascades for the synthesis of catecholamines and other CNS neurotransmitters. The conversion from L-Tyrosine to L-DOPA is dependent upon the catalytic action of Tyrosine Hydroxylase. From there, L-DOPA can make Dopamine and eventually Epinephrine and Norepinephrine as well. <br /> <br /> [[File:Catecholamine_Synthesis.jpg|500px|thumb|right|Cascade of Catecholamine Synthesis]]<br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2291442/<br /> https://www.ncbi.nlm.nih.gov/pubmed/19396395<br /> <br /> ===Abnormalities/abnormal development===<br /> ----<br /> ===Animal models===<br /> ----<br /> Animal models are an integral part of research in embryology. In particular due to the moral concerns regarding the use of humans in scientific research. As a result different animals are used as substitutes to simulate the same environments and hope to achieve results that would also be able to represent humans as well. Prenatal adrenal gland development has been described in a number of scientific reports dating from the 1900s to studies in more recent years. These involved a variety of animal models such as ox, sheep, swine and most commonly mice. <br /> <br /> ====Chromaffin cells =(in rat models)====<br /> There has been extensive research conducted into the adrenal chromaffin cells and their embryological developments. As explained above nueral crest cells are pluripotent meaning they are able to differentiate into multiple different cells. The neural crest cells give rise to chromaffin cells of the adrenal medulla.<br /> <br /> To study the formation process of the adrenal medulla in the embryonic period, we visualized chromaffin cells of rat embryos at 13 to 17 days of gestation using anti-tyrosine hydroxylase (TH) antiserum, and created three-dimensional images from serial tissue sections. Between 13 and 15 days of gestation, TH-positive cells (chromaffin cells) migrated from a group of TH-positive cells present dorsal to the adrenal primordium via the medial cranial end of the adrenal primordium into the adrenal primordium. At or after 16 days of gestation, the adrenal capsule was formed except on the ventral aspect of the cranial end of the adrenal gland, from which TH-positive cells penetrated into the adrenal gland.(Pubmed: 15240937) <br /> <br /> Ahonen suggested that some neural crest cells continue migration from the chain ganglia to the lateral sides of aorta, where they form the perirenal ganglia and adrenal medulla, and finally to the ventral side of the aorta to form the preaortic sympathetic tissue. However, that report only showed the several transverse sections of the fetal trunk for the a demonstration of the migration route of neural crest cells. In this study, using three dimensional reconstructed images, we aimed to observe how TH-labeled chromaffin cells penetrate into the adrenal anlage to form the adrenal medulla and whether the migration route of TH - positive cells from the adrenal connects the preaortic sympathetic ganglia <br /> (M.Yamato, R. Yanai, K. Arishima, 2004) <br /> <br /> Prenatal adrenal gland development has been described in numerous published reports covering a wide variety of species, including the ox (Katznelson, 1966; Wrobel and Suss, 1999), sheep (Davies, 1950; Wintour et al., 1975; Upadhyay and Zamboni, 1982; Naaman‐Reperant and Durand, 1997; Grino, 2004), swine (Sokolov et al., 2006) and mouse (Waring, 1935; Ikeda et al., 1994; Sass, 1996; Nyska and Maronpot, 1999; Bland et al., 2003; Val et al., 2007). Adrenal gland development also has been extensively described for humans as well (Kolliker, 1879; Minot, 1892; Zuckerkandl, 1912; Wieman, 1920; Ikeda et al., 1981; Langlois et al., 2002; Hanley and Arit, 2006).<br /> <br /> https://www.sciencedirect.com/science/article/pii/S0925477302004550<br /> http://dev.biologists.org/content/develop/126/13/2935.full.pdf<br /> <br /> ===Current research (labs)===<br /> ----<br /> The findings presented until now have focused on the mechanisms controlling migration along the dorsolateral path. In comparison, our understanding of the mechanisms controlling NCC migration along the ventral path are complicated by the fact that this population comprises multiple precursors that form different derivatives in distinct regions of the embryo. For example, ventrally migrating NCCs either stop within the sclerotome in close association with the neural tube to form neurons and glia of the sensory nervous system (i.e. the dorsal root ganglia [DRG]), while other NCCs continue to migrate further ventrally to form the autonomic nervous system (i.e. sympathetic ganglia and chromaffin cells of the adrenal gland)<br /> <br /> Adrenomedullary chromaffin cells are catecholamine (CA)-producing cells originating from trunk neural crest (NC) via sympathoadrenal progenitors (SAPs). We generated NC and SAPs from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) in vitro via BMP2/FGF2 exposure, ascertained by qPCR and immunoexpression of SOX10, ASCL1, TFAP2α, and PHOX2B, and by fluorescence-activated cell sorting selection for p75NTR and GD2, and confirmed their trunk-like HOX gene expression. We showed that continuing BMP4 and curtailing FGF2 in vitro, augmented with corticosteroid mimetic, induced these cells to upregulate the chromaffin cell-specific marker PNMT and other CA synthesis and storage markers, and we demonstrated noradrenaline and adrenaline by Faglu and high-performance liquid chromatography. We showed these human cells' SAP-like property of migration and differentiation into cells expressing chromaffin cell markers by implanting them into avian embryos in vivo and in chorio-allantoic membrane grafts. These cells have the potential for investigating differentiation of human chromaffin cells and for modeling diseases involving this cell type.<br /> <br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768882/<br /> <br /> ===Glossary===<br /> ----<br /> ===Reference list===</div>

Z5091101 https://embryology.med.unsw.edu.au/embryology/index.php?title=2018_Group_Project_1&diff=355713 2018 Group Project 1 2018-10-07T09:26:31Z

<p>Z5091101: /* History */</p> <hr /> <div>=The Contribution of Neural Crest Cells to the Adrenal Medulla=<br /> ----<br /> {{2018ANAT2341ProjectHeader}}<br /> <br /> <br /> ===Introduction===<br /> [[User:Z5014972|Z5014972]] ([[User talk:Z5014972|talk]]) 12:47, 14 August 2018 (AEST)z5014972 <br /> good review article https://link.springer.com/article/10.1007%2Fs12022-009-9070-6<br /> ----<br /> ===History===<br /> ----<br /> '''Describing the neural crest'''<br /> [[File:Wilhelm_His_History_Wilhelm.jpeg|left|230px|thumb|Wilhelm His]]<br /> The "neural crest" is a structure in the embryo and is the junction between the neural and epidermal ectoderm. It is exclusive to vertebrates and forms a range of structures{{#pmid:22230617|PMID22230617}}. The neural crest contributes a large number of cells of varying structure and function that directly or indirectly contribute to the development of tissues and organs within the body {{#pmid:19179766|PMID19179766}}. In 1868, the neural crest cells were first identified in a chick embryo as a collection of cells known as "Zwischenstrang" by Professor Wilhelm His {{#pmid:22820859|PMID22820859}}. Wilhelm His was among the first to provide an explanation for the mechanics governing the developing embryo as well as the physiology and the organs that the differing germinal regions would eventually give rise to. In 1878, the term neural ridge was used to describe this collection of cells but the term neural crest was later coined by Arthur Milnes Marshall in 1879 in a paper he worked on disseminating the knowledge from his research on the development of cranial nerves in chicken embryos. {{#pmid:19179766|PMID19179766}}.<br /> [[File:NC Location.jpg|left|450px|thumb|The neural crest]]<br /> <br /> '''1890s-1950s'''<br /> The neural crest is the point of origin for spinal/cranial ganglia and neurons. This theory received little criticism and was not contested much by other researchers prior to the 1890s. This is owing to the fact that the neural crest is quite closely related to the neural tube and thus this relationship makes sense. This discovery was made by His and Marshall, however, they found this out independently of one another.In the 1890s, Julia Platt, claimed that odontoblasts as well as the cartilages forming the facial and pharyngeal arch skeletons came from the ectoderm. This created much debate and was contested by many{{#pmid:22820859|PMID22820859}}. <br /> <br /> This is because this theory completely contradicted the germ-layer theory, whereby skeletal tissues originate at the mesoderm and not the ectoderm. The controversies this finding created brought about a slowing down of research, as demonstrated by a gap of almost 40 years between the theory that skeletal tissues originating from the neural crest. Today, it is known that the neural crest does indeed play a role in the development of the skeleton in vertebrates, particularly, the cranial neural crest. Although these studies were occurring, the focus was still primarily on researching pigment cells and ganglia of the spine up until the 1950s, when Sven Hörstadius' major work on the neural crest was published, titled "The Neural Crest: Its properties and derivatives in the light of experimental research". This work focused on experimental data tracing the development of the cartilaginous skeleton derived from the neural crest {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1960s - 1970s'''<br /> In the 1960s, the migration patterns of neural crest cells were studied in avian embryos (birds). This was a shift from studying the embryos of amphibians. This was inspired by studies conducted in the 1960s on neural crest cells migrating from the brain and spinal cord, known as trunk and cranial neural crest cells {{#pmid:19179766|PMID19179766}}. The cranial neural crest eventually becomes the bones, cartilage and connective tissues forming the foundation of the face, ears and teeth. The trunk neural crest cells can either become melanocytes or can migrate into sclerotomes which are later contributors to the cartilage of the spine and the dorsal root ganglia {{#pmid:22820859|PMID22820859}}. The cells in the trunk neural crest that migrate vertically become the sympathetic ganglia, the nerves proximal to the aorta and the adrenal medulla <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. In the 1970s many detailed maps signifying the pathways of many of the neural crest cells appeared as well as an understanding that the environment in which the neural crest cells are found plays a major role in their final development as well as the occurrences of abnormalities in the fetus {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1980s - 21st century'''<br /> [[File:Regions_of_NC_Cells.jpg|left|Neural crest regions|thumb]]<br /> From the 1980s-1990s, the causative agent of organ transformation from one to another (homeotic patterning), as well as the Hox genes which regulate the axis of most symmetrical animal embryos were founded and studied. The neural crest, which previously was divided into the cranial and trunk regions, was now further divided into the vagal and sacral neural crest, the cardiac neural crest and the cephalic neural crest {{#pmid:19179766|PMID19179766}}. The vagal & sacral neural crest gives rise to the parasympathetic ganglia found in the gut. Without these ganglia, peristalsis, is not possible <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. The cardiac neural crest contributes to the valves, septa and major blood vessels of the heart, as well as connective tissues and cartilage{{#pmid:19179766|PMID19179766}}. This is important for the structure of the heart as well as its overall function, enabling it to move blood around the body efficiently as well as keep pulmonary and aortic circulation separated <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> <br /> <br /> Today, knowledge of the neural crest cells, their migration patterns, modes of differentiation, derivatives and apoptosis (cell death) are being studied extensively. This is being done on a comparative basis between different organisms, to add further evidence for evolution {{#pmid:19179766|PMID19179766}}. The neural crest is definitely forging a "crest" between the fields of developmental and evolutionary biology, as it is a structure '''shared exclusively by all vertebrates'''. Invertebrates do not derive their specialised cells from the neural crest as they do not have one, rather, they derive these from the endomesoderm {{#pmid:22230617|PMID22230617}}.<br /> <br /> '''Future directions'''<br /> <br /> Since its discovery by His, the neural crest field has made great progress, from studies performed on the structure, to analysis of the molecules and whether certain aspects of the neural crest are specific to a single species of organism, or to all vertebrates collectively. Future work on the cranial neural crest needs to be done as well as identifying and categorising the networks responsible for the proliferation and death of cells, as well as how the cells move and migrate, as well as the gene regulatory networks (GRNs) that regulate the synthesis of proteins. Advances in technology will undeniable lead us to more answers on the subject {{#pmid:22230617|PMID22230617}}.<br /> <br /> ===Embryonic origins===<br /> ----<br /> https://www.ncbi.nlm.nih.gov/books/NBK10065/<br /> <br /> ===Developmental time course===<br /> ----<br /> <br /> The adrenal gland has two distinct sections, the cortex and the medulla, both with different embryonic origins. The cortex accounts for 90% of the adrenal glands and arises from intermediate mesoderm. The medulla only accounts for 10% of the adult adrenal glands, however it has neural crest embryonic origin. The medulla consists of chromaffinoblast cells which are migrant neuroblast cells from the neural crest, therefore the adrenal medulla is a component of the sympathetic nervous system.{{#pmid:21175739|PMID21175739}} Neural crest cells replicate in week 7 and begin to differentiate in week 8, the cells then migrate to the developing adrenal gland in week 9 of development.{{#pmid:25255746|PMID25255746}}{{#pmid:18279781|PMID18279781}} The neural crest cells infiltrate the cortex and the chromaffin cells are scattered islands in the cortex.{{#pmid:23354096|PMID23354096}} Throughout development the cells will become more compact in the centre of the gland, during this period of development the adrenal gland is growing rapidly. The gland is abnormally large until the second trimester and the medulla is much thicker prenatally.{{#pmid:18279781|PMID18279781}}{{#pmid:21175739|PMID21175739}}<br /> <br /> ===Developmental/adult function===<br /> ----<br /> ===Tissue/organ structure===<br /> <br /> ====Normal Structure and Function of the Adrenal Medulla====<br /> <br /> The cells of the adrenal medulla are derived from the neural crest as opposed to the mesodermal origins of the cortex. The medulla contains secretory cells called chromaffin cells, due to the agents they produce when oxidised, such as chromate. These cells secrete epinephrine and norepinephrine in response to various substances such as acetylcholine.<br /> <br /> There are three types of cells in the adult adrenal medulla: <br /> 1) Epinephrine cells<br /> 2) Norepinephrine cells <br /> 3) Small granule-containing cells (SGCs)<br /> These cells also produce various other peptides such as substance P and neurotensin. The adrenal medulla also contains presynaptic sympathetic ganglion cells. <br /> <br /> <br /> ====Related Anatomy====<br /> <br /> The tissue and organ structure of the adrenal medulla should be understood with regard to its specialised function within the sympathetic nervous system. <br /> <br /> The medullary region of the adrenal glands is tasked with the endocrine secretions of adrenaline and nor-adrenaline in response to environmental stressors that are signalled for by the sympathetic nervous system. That is, the secretion of fight-or-flight response hormones in order to restrict vasculature to the trunk and increase vascular activity in the peripheral musculature.<br /> <br /> The adrenal glands are supplied by several branches of the great vessels in the abdominal cavity. The secreted catecholamines in the medulla are directly able to pass to the blood stream this way.<br /> <br /> These adrenal glands and their contents are retroperitoneal in the adult and varied in shape, with the left often being semilunar and right being pyramidal. Nervous supply of the adrenal glands is achieved by contributions from the splanchnic nerves of the celiac plexus. <br /> <br /> <br /> [[File:Dd.jpg|500px|thumb|right|Adult Adrenal Glands in situ]] <br /> ----<br /> <br /> ===Molecular mechanisms/factors/genes===<br /> ----<br /> <br /> ====Role of Adrenal Medulla in the Neonate and Adult====<br /> <br /> Understanding the biochemistry of catecholamines is necessary to see how the adrenal medulla is designed in the stages of embryology and how it is suited for life in the neonate and adult. <br /> <br /> The epinephrine and norepinephrine in the neonate and adult work by primarily changing the osmoregulatory state of vasculature in organs. With the exclusion of their neuromodulatory and neurotransmitter functions, epinephrine and norepinephrine are mainly tasked with the control of sympathetic and parasympathetic supplies. <br /> <br /> >Norepinephrine is a constrictor of peripheral vasculature by antagonising the action of surface receptors expressed on the endothelium of blood vessels, specifically Alpha-1 and Alpha-2 receptors, such that vascular resistance increases. <br /> <br /> >Epinephrine is both a vasoconstrictor and vasodilator, depending on what receptors it attaches to. As a non-selective adrenergic agonist, it acts on Alpha-1, Alpha-2, Beta-1, Beta-2 and Beta-3 receptors that are found throughout the body's tissues, yielding many different physiological responses.<br /> <br /> ====Genes and Transcription Factors Involved with the Adrenal Medulla's Development====<br /> <br /> Members of the SOX (SRY-Box) gene family have multiple key contributors to Neural Crest in the Adrenal Medulla.<br /> <br /> Mouse models have demonstrated that SOX-10 knock-outs (mice whose DNA has been engineered to not express SOX-10) do not have an adrenal medulla. There has also been suggestion that SOX-8,9 and 10 are all strongly related to the migratory patterning of neural crest cells to the developing adrenal glands.<br /> <br /> The TH gene (for Tyrosine Hydroxylase) encodes the aforementioned enzyme in the adrenal medulla and central nervous system. Tyrosine Hydroxylase is crucial in biochemical pathways and cascades for the synthesis of catecholamines and other CNS neurotransmitters. The conversion from L-Tyrosine to L-DOPA is dependent upon the catalytic action of Tyrosine Hydroxylase. From there, L-DOPA can make Dopamine and eventually Epinephrine and Norepinephrine as well. <br /> <br /> [[File:Catecholamine_Synthesis.jpg|500px|thumb|right|Cascade of Catecholamine Synthesis]]<br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2291442/<br /> https://www.ncbi.nlm.nih.gov/pubmed/19396395<br /> <br /> ===Abnormalities/abnormal development===<br /> ----<br /> ===Animal models===<br /> ----<br /> Animal models are an integral part of research in embryology. In particular due to the moral concerns regarding the use of humans in scientific research. As a result different animals are used as substitutes to simulate the same environments and hope to achieve results that would also be able to represent humans as well. Prenatal adrenal gland development has been described in a number of scientific reports dating from the 1900s to studies in more recent years. These involved a variety of animal models such as ox, sheep, swine and most commonly mice. <br /> <br /> <br /> There has been extensive research conducted into the adrenal chromaffin cells and their embryological developments. As explained above nueral crest cells are pluripotent meaning they are able to differentiate into multiple different cells. The neural crest cells give rise to chromaffin cells of the adrenal medulla.<br /> Ahonen suggested that some neural crest cells continue migration from the chain ganglia to the lateral sides of aorta, where they form the perirenal ganglia and adrenal medulla, and finally to the ventral side of the aorta to form the preaortic sympathetic tissue. However, that report only showed the several transverse sections of the fetal trunk for the a demonstration of the migration route of neural crest cells. In this study, using three dimensional reconstructed images, we aimed to observe how TH-labeled chromaffin cells penetrate into the adrenal anlage to form the adrenal medulla and whether the migration route of TH - positive cells from the adrenal connects the preaortic sympathetic ganglia <br /> (M.Yamato, R. Yanai, K. Arishima, 2004) <br /> <br /> Prenatal adrenal gland development has been described in numerous published reports covering a wide variety of species, including the ox (Katznelson, 1966; Wrobel and Suss, 1999), sheep (Davies, 1950; Wintour et al., 1975; Upadhyay and Zamboni, 1982; Naaman‐Reperant and Durand, 1997; Grino, 2004), swine (Sokolov et al., 2006) and mouse (Waring, 1935; Ikeda et al., 1994; Sass, 1996; Nyska and Maronpot, 1999; Bland et al., 2003; Val et al., 2007). Adrenal gland development also has been extensively described for humans as well (Kolliker, 1879; Minot, 1892; Zuckerkandl, 1912; Wieman, 1920; Ikeda et al., 1981; Langlois et al., 2002; Hanley and Arit, 2006).<br /> <br /> https://www.sciencedirect.com/science/article/pii/S0925477302004550<br /> http://dev.biologists.org/content/develop/126/13/2935.full.pdf<br /> <br /> ===Current research (labs)===<br /> ----<br /> The findings presented until now have focused on the mechanisms controlling migration along the dorsolateral path. In comparison, our understanding of the mechanisms controlling NCC migration along the ventral path are complicated by the fact that this population comprises multiple precursors that form different derivatives in distinct regions of the embryo. For example, ventrally migrating NCCs either stop within the sclerotome in close association with the neural tube to form neurons and glia of the sensory nervous system (i.e. the dorsal root ganglia [DRG]), while other NCCs continue to migrate further ventrally to form the autonomic nervous system (i.e. sympathetic ganglia and chromaffin cells of the adrenal gland)<br /> <br /> Adrenomedullary chromaffin cells are catecholamine (CA)-producing cells originating from trunk neural crest (NC) via sympathoadrenal progenitors (SAPs). We generated NC and SAPs from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) in vitro via BMP2/FGF2 exposure, ascertained by qPCR and immunoexpression of SOX10, ASCL1, TFAP2α, and PHOX2B, and by fluorescence-activated cell sorting selection for p75NTR and GD2, and confirmed their trunk-like HOX gene expression. We showed that continuing BMP4 and curtailing FGF2 in vitro, augmented with corticosteroid mimetic, induced these cells to upregulate the chromaffin cell-specific marker PNMT and other CA synthesis and storage markers, and we demonstrated noradrenaline and adrenaline by Faglu and high-performance liquid chromatography. We showed these human cells' SAP-like property of migration and differentiation into cells expressing chromaffin cell markers by implanting them into avian embryos in vivo and in chorio-allantoic membrane grafts. These cells have the potential for investigating differentiation of human chromaffin cells and for modeling diseases involving this cell type.<br /> <br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768882/<br /> <br /> ===Glossary===<br /> ----<br /> ===Reference list===</div>

Z5091101 https://embryology.med.unsw.edu.au/embryology/index.php?title=2018_Group_Project_1&diff=355711 2018 Group Project 1 2018-10-07T09:02:50Z

<p>Z5091101: /* History */</p> <hr /> <div>=The Contribution of Neural Crest Cells to the Adrenal Medulla=<br /> ----<br /> {{2018ANAT2341ProjectHeader}}<br /> <br /> <br /> ===Introduction===<br /> [[User:Z5014972|Z5014972]] ([[User talk:Z5014972|talk]]) 12:47, 14 August 2018 (AEST)z5014972 <br /> good review article https://link.springer.com/article/10.1007%2Fs12022-009-9070-6<br /> ----<br /> ===History===<br /> ----<br /> '''Describing the neural crest'''<br /> [[File:Wilhelm_His_History_Wilhelm.jpeg|left|230px|thumb|Wilhelm His]]<br /> The "neural crest" is a structure in the embryo and is the junction between the neural and epidermal ectoderm. The neural crest contributes a large number of cells of varying structure and function that directly or indirectly contribute to the development of tissues and organs within the body {{#pmid:19179766|PMID19179766}}. In 1868, the neural crest cells were first identified in a chick embryo as a collection of cells known as "Zwischenstrang" by Professor Wilhelm His {{#pmid:22820859|PMID22820859}}. Wilhelm His was among the first to provide an explanation for the mechanics governing the developing embryo as well as the physiology and the organs that the differing germinal regions would eventually give rise to. In 1878, the term neural ridge was used to describe this collection of cells but the term neural crest was later coined by Arthur Milnes Marshall in 1879 in a paper he worked on disseminating the knowledge from his research on the development of cranial nerves in chicken embryos. {{#pmid:19179766|PMID19179766}}.<br /> [[File:NC Location.jpg|left|450px|thumb|The neural crest]]<br /> <br /> '''1890s-1950s'''<br /> The neural crest is the point of origin for spinal/cranial ganglia and neurons. This theory received little criticism and was not contested much by other researchers prior to the 1890s. This is owing to the fact that the neural crest is quite closely related to the neural tube and thus this relationship makes sense. This discovery was made by His and Marshall, however, they found this out independently of one another.In the 1890s, Julia Platt, claimed that odontoblasts as well as the cartilages forming the facial and pharyngeal arch skeletons came from the ectoderm. This created much debate and was contested by many{{#pmid:22820859|PMID22820859}}. <br /> <br /> This is because this theory completely contradicted the germ-layer theory, whereby skeletal tissues originate at the mesoderm and not the ectoderm. The controversies this finding created brought about a slowing down of research, as demonstrated by a gap of almost 40 years between the theory that skeletal tissues originating from the neural crest. Today, it is known that the neural crest does indeed play a role in the development of the skeleton in vertebrates, particularly, the cranial neural crest. Although these studies were occurring, the focus was still primarily on researching pigment cells and ganglia of the spine up until the 1950s, when Sven Hörstadius' major work on the neural crest was published, titled "The Neural Crest: Its properties and derivatives in the light of experimental research". This work focused on experimental data tracing the development of the cartilaginous skeleton derived from the neural crest {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1960s - 1970s'''<br /> In the 1960s, the migration patterns of neural crest cells were studied in avian embryos (birds). This was a shift from studying the embryos of amphibians. This was inspired by studies conducted in the 1960s on neural crest cells migrating from the brain and spinal cord, known as trunk and cranial neural crest cells {{#pmid:19179766|PMID19179766}}. The cranial neural crest eventually becomes the bones, cartilage and connective tissues forming the foundation of the face, ears and teeth. The trunk neural crest cells can either become melanocytes or can migrate into sclerotomes which are later contributors to the cartilage of the spine and the dorsal root ganglia {{#pmid:22820859|PMID22820859}}. The cells in the trunk neural crest that migrate vertically become the sympathetic ganglia, the nerves proximal to the aorta and the adrenal medulla <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. In the 1970s many detailed maps signifying the pathways of many of the neural crest cells appeared as well as an understanding that the environment in which the neural crest cells are found plays a major role in their final development as well as the occurrences of abnormalities in the fetus {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1980s - 21st century'''<br /> [[File:Regions_of_NC_Cells.jpg|left|Neural crest regions|thumb]]<br /> From the 1980s-1990s, the causative agent of organ transformation from one to another (homeotic patterning), as well as the Hox genes which regulate the axis of most symmetrical animal embryos were founded and studied. The neural crest, which previously was divided into the cranial and trunk regions, was now further divided into the vagal and sacral neural crest, the cardiac neural crest and the cephalic neural crest {{#pmid:19179766|PMID19179766}}. The vagal & sacral neural crest gives rise to the parasympathetic ganglia found in the gut. Without these ganglia, peristalsis, is not possible <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. The cardiac neural crest contributes to the valves, septa and major blood vessels of the heart, as well as connective tissues and cartilage{{#pmid:19179766|PMID19179766}}. This is important for the structure of the heart as well as its overall function, enabling it to move blood around the body efficiently as well as keep pulmonary and aortic circulation separated <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> <br /> <br /> Today, knowledge of the neural crest cells, their migration patterns, modes of differentiation, derivatives and apoptosis (cell death) are being studied extensively. This is being done on a comparative basis between different organisms, to add further evidence for evolution {{#pmid:19179766|PMID19179766}}. The neural crest is definitely forging a "crest" between the fields of developmental and evolutionary biology, as it is a structure '''shared exclusively by all vertebrates'''. Invertebrates do not derive their specialised cells from the neural crest as they do not have one, rather, they derive these from the endomesoderm {{#pmid:22230617|PMID22230617}}.<br /> <br /> '''Future directions'''<br /> <br /> Since its discovery by His, the neural crest field has made great progress, from studies performed on the structure, to analysis of the molecules and whether certain aspects of the neural crest are specific to a single species of organism, or to all vertebrates collectively. Future work on the cranial neural crest needs to be done as well as identifying and categorising the networks responsible for the proliferation and death of cells, as well as how the cells move and migrate, as well as the gene regulatory networks (GRNs) that regulate the synthesis of proteins. Advances in technology will undeniable lead us to more answers on the subject {{#pmid:22230617|PMID22230617}}.<br /> <br /> ===Embryonic origins===<br /> ----<br /> https://www.ncbi.nlm.nih.gov/books/NBK10065/<br /> <br /> ===Developmental time course===<br /> ----<br /> <br /> The adrenal gland has two distinct sections, the cortex and the medulla, both with different embryonic origins. The cortex accounts for 90% of the adrenal glands and arises from intermediate mesoderm. The medulla only accounts for 10% of the adult adrenal glands, however it has neural crest embryonic origin. The medulla consists of chromaffinoblast cells which are migrant neuroblast cells from the neural crest, therefore the adrenal medulla is a component of the sympathetic nervous system.{{#pmid:21175739|PMID21175739}} Neural crest cells replicate in week 7 and begin to differentiate in week 8, the cells then migrate to the developing adrenal gland in week 9 of development.{{#pmid:25255746|PMID25255746}}{{#pmid:18279781|PMID18279781}} The neural crest cells infiltrate the cortex and the chromaffin cells are scattered islands in the cortex.{{#pmid:23354096|PMID23354096}} Throughout development the cells will become more compact in the centre of the gland, during this period of development the adrenal gland is growing rapidly. The gland is abnormally large until the second trimester and the medulla is much thicker prenatally.{{#pmid:18279781|PMID18279781}}{{#pmid:21175739|PMID21175739}}<br /> <br /> ===Developmental/adult function===<br /> ----<br /> ===Tissue/organ structure===<br /> <br /> ====Normal Structure and Function of the Adrenal Medulla====<br /> <br /> The cells of the adrenal medulla are derived from the neural crest as opposed to the mesodermal origins of the cortex. The medulla contains secretory cells called chromaffin cells, due to the agents they produce when oxidised, such as chromate. These cells secrete epinephrine and norepinephrine in response to various substances such as acetylcholine.<br /> <br /> There are three types of cells in the adult adrenal medulla: <br /> 1) Epinephrine cells<br /> 2) Norepinephrine cells <br /> 3) Small granule-containing cells (SGCs)<br /> These cells also produce various other peptides such as substance P and neurotensin. The adrenal medulla also contains presynaptic sympathetic ganglion cells. <br /> <br /> <br /> ====Related Anatomy====<br /> <br /> The tissue and organ structure of the adrenal medulla should be understood with regard to its specialised function within the sympathetic nervous system. <br /> <br /> The medullary region of the adrenal glands is tasked with the endocrine secretions of adrenaline and nor-adrenaline in response to environmental stressors that are signalled for by the sympathetic nervous system. That is, the secretion of fight-or-flight response hormones in order to restrict vasculature to the trunk and increase vascular activity in the peripheral musculature.<br /> <br /> The adrenal glands are supplied by several branches of the great vessels in the abdominal cavity. The secreted catecholamines in the medulla are directly able to pass to the blood stream this way.<br /> <br /> These adrenal glands and their contents are retroperitoneal in the adult and varied in shape, with the left often being semilunar and right being pyramidal. Nervous supply of the adrenal glands is achieved by contributions from the splanchnic nerves of the celiac plexus. <br /> <br /> <br /> [[File:Dd.jpg|500px|thumb|right|Adult Adrenal Glands in situ]] <br /> ----<br /> <br /> ===Molecular mechanisms/factors/genes===<br /> ----<br /> <br /> ====Role of Adrenal Medulla in the Neonate and Adult====<br /> <br /> Understanding the biochemistry of catecholamines is necessary to see how the adrenal medulla is designed in the stages of embryology and how it is suited for life in the neonate and adult. <br /> <br /> The epinephrine and norepinephrine in the neonate and adult work by primarily changing the osmoregulatory state of vasculature in organs. With the exclusion of their neuromodulatory and neurotransmitter functions, epinephrine and norepinephrine are mainly tasked with the control of sympathetic and parasympathetic supplies. <br /> <br /> >Norepinephrine is a constrictor of peripheral vasculature by antagonising the action of surface receptors expressed on the endothelium of blood vessels, specifically Alpha-1 and Alpha-2 receptors, such that vascular resistance increases. <br /> <br /> >Epinephrine is both a vasoconstrictor and vasodilator, depending on what receptors it attaches to. As a non-selective adrenergic agonist, it acts on Alpha-1, Alpha-2, Beta-1, Beta-2 and Beta-3 receptors that are found throughout the body's tissues, yielding many different physiological responses.<br /> <br /> ====Genes and Transcription Factors Involved with the Adrenal Medulla's Development====<br /> <br /> Members of the SOX (SRY-Box) gene family have multiple key contributors to Neural Crest in the Adrenal Medulla.<br /> <br /> Mouse models have demonstrated that SOX-10 knock-outs (mice whose DNA has been engineered to not express SOX-10) do not have an adrenal medulla. There has also been suggestion that SOX-8,9 and 10 are all strongly related to the migratory patterning of neural crest cells to the developing adrenal glands.<br /> <br /> The TH gene (for Tyrosine Hydroxylase) encodes the aforementioned enzyme in the adrenal medulla and central nervous system. Tyrosine Hydroxylase is crucial in biochemical pathways and cascades for the synthesis of catecholamines and other CNS neurotransmitters. The conversion from L-Tyrosine to L-DOPA is dependent upon the catalytic action of Tyrosine Hydroxylase. From there, L-DOPA can make Dopamine and eventually Epinephrine and Norepinephrine as well. <br /> <br /> [[File:Catecholamine_Synthesis.jpg|500px|thumb|right|Cascade of Catecholamine Synthesis]]<br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2291442/<br /> https://www.ncbi.nlm.nih.gov/pubmed/19396395<br /> <br /> ===Abnormalities/abnormal development===<br /> ----<br /> ===Animal models===<br /> ----<br /> Animal models are an integral part of research in embryology. In particular due to the moral concerns regarding the use of humans in scientific research. As a result different animals are used as substitutes to simulate the same environments and hope to achieve results that would also be able to represent humans as well. Prenatal adrenal gland development has been described in a number of scientific reports dating from the 1900s to studies in more recent years. These involved a variety of animal models such as ox, sheep, swine and most commonly mice. <br /> <br /> <br /> There has been extensive research conducted into the adrenal chromaffin cells and their embryological developments. As explained above nueral crest cells are pluripotent meaning they are able to differentiate into multiple different cells. The neural crest cells give rise to chromaffin cells of the adrenal medulla.<br /> Ahonen suggested that some neural crest cells continue migration from the chain ganglia to the lateral sides of aorta, where they form the perirenal ganglia and adrenal medulla, and finally to the ventral side of the aorta to form the preaortic sympathetic tissue. However, that report only showed the several transverse sections of the fetal trunk for the a demonstration of the migration route of neural crest cells. In this study, using three dimensional reconstructed images, we aimed to observe how TH-labeled chromaffin cells penetrate into the adrenal anlage to form the adrenal medulla and whether the migration route of TH - positive cells from the adrenal connects the preaortic sympathetic ganglia <br /> (M.Yamato, R. Yanai, K. Arishima, 2004) <br /> <br /> Prenatal adrenal gland development has been described in numerous published reports covering a wide variety of species, including the ox (Katznelson, 1966; Wrobel and Suss, 1999), sheep (Davies, 1950; Wintour et al., 1975; Upadhyay and Zamboni, 1982; Naaman‐Reperant and Durand, 1997; Grino, 2004), swine (Sokolov et al., 2006) and mouse (Waring, 1935; Ikeda et al., 1994; Sass, 1996; Nyska and Maronpot, 1999; Bland et al., 2003; Val et al., 2007). Adrenal gland development also has been extensively described for humans as well (Kolliker, 1879; Minot, 1892; Zuckerkandl, 1912; Wieman, 1920; Ikeda et al., 1981; Langlois et al., 2002; Hanley and Arit, 2006).<br /> <br /> https://www.sciencedirect.com/science/article/pii/S0925477302004550<br /> http://dev.biologists.org/content/develop/126/13/2935.full.pdf<br /> <br /> ===Current research (labs)===<br /> ----<br /> The findings presented until now have focused on the mechanisms controlling migration along the dorsolateral path. In comparison, our understanding of the mechanisms controlling NCC migration along the ventral path are complicated by the fact that this population comprises multiple precursors that form different derivatives in distinct regions of the embryo. For example, ventrally migrating NCCs either stop within the sclerotome in close association with the neural tube to form neurons and glia of the sensory nervous system (i.e. the dorsal root ganglia [DRG]), while other NCCs continue to migrate further ventrally to form the autonomic nervous system (i.e. sympathetic ganglia and chromaffin cells of the adrenal gland)<br /> <br /> Adrenomedullary chromaffin cells are catecholamine (CA)-producing cells originating from trunk neural crest (NC) via sympathoadrenal progenitors (SAPs). We generated NC and SAPs from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) in vitro via BMP2/FGF2 exposure, ascertained by qPCR and immunoexpression of SOX10, ASCL1, TFAP2α, and PHOX2B, and by fluorescence-activated cell sorting selection for p75NTR and GD2, and confirmed their trunk-like HOX gene expression. We showed that continuing BMP4 and curtailing FGF2 in vitro, augmented with corticosteroid mimetic, induced these cells to upregulate the chromaffin cell-specific marker PNMT and other CA synthesis and storage markers, and we demonstrated noradrenaline and adrenaline by Faglu and high-performance liquid chromatography. We showed these human cells' SAP-like property of migration and differentiation into cells expressing chromaffin cell markers by implanting them into avian embryos in vivo and in chorio-allantoic membrane grafts. These cells have the potential for investigating differentiation of human chromaffin cells and for modeling diseases involving this cell type.<br /> <br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768882/<br /> <br /> ===Glossary===<br /> ----<br /> ===Reference list===</div>

Z5091101 https://embryology.med.unsw.edu.au/embryology/index.php?title=2018_Group_Project_1&diff=355709 2018 Group Project 1 2018-10-07T08:56:52Z

<p>Z5091101: /* History */</p> <hr /> <div>=The Contribution of Neural Crest Cells to the Adrenal Medulla=<br /> ----<br /> {{2018ANAT2341ProjectHeader}}<br /> <br /> <br /> ===Introduction===<br /> [[User:Z5014972|Z5014972]] ([[User talk:Z5014972|talk]]) 12:47, 14 August 2018 (AEST)z5014972 <br /> good review article https://link.springer.com/article/10.1007%2Fs12022-009-9070-6<br /> ----<br /> ===History===<br /> ----<br /> '''Describing the neural crest'''<br /> [[File:Wilhelm_His_History_Wilhelm.jpeg|left|230px|thumb|Wilhelm His]]<br /> The "neural crest" is a structure in the embryo and is the junction between the neural and epidermal ectoderm. The neural crest contributes a large number of cells of varying structure and function that directly or indirectly contribute to the development of tissues and organs within the body {{#pmid:19179766|PMID19179766}}. In 1868, the neural crest cells were first identified in a chick embryo as a collection of cells known as "Zwischenstrang" by Professor Wilhelm His {{#pmid:22820859|PMID22820859}}. Wilhelm His was among the first to provide an explanation for the mechanics governing the developing embryo as well as the physiology and the organs that the differing germinal regions would eventually give rise to. In 1878, the term neural ridge was used to describe this collection of cells but the term neural crest was later coined by Arthur Milnes Marshall in 1879 in a paper he worked on disseminating the knowledge from his research on the development of cranial nerves in chicken embryos. {{#pmid:19179766|PMID19179766}}.<br /> [[File:NC Location.jpg|left|450px|thumb|The neural crest]]<br /> <br /> '''1890s-1950s'''<br /> The neural crest is the point of origin for spinal/cranial ganglia and neurons. This theory received little criticism and was not contested much by other researchers prior to the 1890s. This is owing to the fact that the neural crest is quite closely related to the neural tube and thus this relationship makes sense. This discovery was made by His and Marshall, however, they found this out independently of one another.In the 1890s, Julia Platt, claimed that odontoblasts as well as the cartilages forming the facial and pharyngeal arch skeletons came from the ectoderm. This created much debate and was contested by many. <br /> <br /> This is because this theory completely contradicted the germ-layer theory, whereby skeletal tissues originate at the mesoderm and not the ectoderm. The controversies this finding created brought about a slowing down of research, as demonstrated by a gap of almost 40 years between the theory that skeletal tissues originating from the neural crest. Today, it is known that the neural crest does indeed play a role in the development of the skeleton in vertebrates, particularly, the cranial neural crest. Although these studies were occurring, the focus was still primarily on researching pigment cells and ganglia of the spine up until the 1950s, when Sven Hörstadius' major work on the neural crest was published, titled "The Neural Crest: Its properties and derivatives in the light of experimental research". This work focused on experimental data tracing the development of the cartilaginous skeleton derived from the neural crest {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1960s - 1970s'''<br /> In the 1960s, the migration patterns of neural crest cells were studied in avian embryos (birds). This was a shift from studying the embryos of amphibians. This was inspired by studies conducted in the 1960s on neural crest cells migrating from the brain and spinal cord, known as trunk and cranial neural crest cells {{#pmid:19179766|PMID19179766}}. The cranial neural crest eventually becomes the bones, cartilage and connective tissues forming the foundation of the face, ears and teeth. The trunk neural crest cells can either become melanocytes or can migrate into sclerotomes which are later contributors to the cartilage of the spine and the dorsal root ganglia {{#pmid:22820859|PMID22820859}}. The cells in the trunk neural crest that migrate vertically become the sympathetic ganglia, the nerves proximal to the aorta and the adrenal medulla <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. In the 1970s many detailed maps signifying the pathways of many of the neural crest cells appeared as well as an understanding that the environment in which the neural crest cells are found plays a major role in their final development as well as the occurrences of abnormalities in the fetus {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1980s - 21st century'''<br /> [[File:Regions_of_NC_Cells.jpg|left|Neural crest regions|thumb]]<br /> From the 1980s-1990s, the causative agent of organ transformation from one to another (homeotic patterning), as well as the Hox genes which regulate the axis of most symmetrical animal embryos were founded and studied. The neural crest, which previously was divided into the cranial and trunk regions, was now further divided into the vagal and sacral neural crest, the cardiac neural crest and the cephalic neural crest {{#pmid:19179766|PMID19179766}}. The vagal & sacral neural crest gives rise to the parasympathetic ganglia found in the gut. Without these ganglia, peristalsis, is not possible <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. The cardiac neural crest contributes to the valves, septa and major blood vessels of the heart, as well as connective tissues and cartilage{{#pmid:19179766|PMID19179766}}. This is important for the structure of the heart as well as its overall function, enabling it to move blood around the body efficiently as well as keep pulmonary and aortic circulation separated <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> <br /> <br /> Today, knowledge of the neural crest cells, their migration patterns, modes of differentiation, derivatives and apoptosis (cell death) are being studied extensively. This is being done on a comparative basis between different organisms, to add further evidence for evolution {{#pmid:19179766|PMID19179766}}. The neural crest is definitely forging a "crest" between the fields of developmental and evolutionary biology, as it is a structure '''shared exclusively by all vertebrates'''. Invertebrates do not derive their specialised cells from the neural crest as they do not have one, rather, they derive these from the endomesoderm {{#pmid:22230617|PMID22230617}}.<br /> <br /> '''Future directions'''<br /> <br /> Since its discovery by His, the neural crest field has made great progress, from studies performed on the structure, to analysis of the molecules and whether certain aspects of the neural crest are specific to a single species of organism, or to all vertebrates collectively. Future work on the cranial neural crest needs to be done as well as identifying and categorising the networks responsible for the proliferation and death of cells, as well as how the cells move and migrate, as well as the gene regulatory networks (GRNs) that regulate the synthesis of proteins. Advances in technology will undeniable lead us to more answers on the subject {{#pmid:22230617|PMID22230617}}.<br /> <br /> ===Embryonic origins===<br /> ----<br /> https://www.ncbi.nlm.nih.gov/books/NBK10065/<br /> <br /> ===Developmental time course===<br /> ----<br /> <br /> The adrenal gland has two distinct sections, the cortex and the medulla, both with different embryonic origins. The cortex accounts for 90% of the adrenal glands and arises from intermediate mesoderm. The medulla only accounts for 10% of the adult adrenal glands, however it has neural crest embryonic origin. The medulla consists of chromaffinoblast cells which are migrant neuroblast cells from the neural crest, therefore the adrenal medulla is a component of the sympathetic nervous system.{{#pmid:21175739|PMID21175739}} Neural crest cells replicate in week 7 and begin to differentiate in week 8, the cells then migrate to the developing adrenal gland in week 9 of development.{{#pmid:25255746|PMID25255746}}{{#pmid:18279781|PMID18279781}} The neural crest cells infiltrate the cortex and the chromaffin cells are scattered islands in the cortex.{{#pmid:23354096|PMID23354096}} Throughout development the cells will become more compact in the centre of the gland, during this period of development the adrenal gland is growing rapidly. The gland is abnormally large until the second trimester and the medulla is much thicker prenatally.{{#pmid:18279781|PMID18279781}}{{#pmid:21175739|PMID21175739}}<br /> <br /> ===Developmental/adult function===<br /> ----<br /> ===Tissue/organ structure===<br /> <br /> ====Normal Structure and Function of the Adrenal Medulla====<br /> <br /> The cells of the adrenal medulla are derived from the neural crest as opposed to the mesodermal origins of the cortex. The medulla contains secretory cells called chromaffin cells, due to the agents they produce when oxidised, such as chromate. These cells secrete epinephrine and norepinephrine in response to various substances such as acetylcholine.<br /> <br /> There are three types of cells in the adult adrenal medulla: <br /> 1) Epinephrine cells<br /> 2) Norepinephrine cells <br /> 3) Small granule-containing cells (SGCs)<br /> These cells also produce various other peptides such as substance P and neurotensin. The adrenal medulla also contains presynaptic sympathetic ganglion cells. <br /> <br /> <br /> ====Related Anatomy====<br /> <br /> The tissue and organ structure of the adrenal medulla should be understood with regard to its specialised function within the sympathetic nervous system. <br /> <br /> The medullary region of the adrenal glands is tasked with the endocrine secretions of adrenaline and nor-adrenaline in response to environmental stressors that are signalled for by the sympathetic nervous system. That is, the secretion of fight-or-flight response hormones in order to restrict vasculature to the trunk and increase vascular activity in the peripheral musculature.<br /> <br /> The adrenal glands are supplied by several branches of the great vessels in the abdominal cavity. The secreted catecholamines in the medulla are directly able to pass to the blood stream this way.<br /> <br /> These adrenal glands and their contents are retroperitoneal in the adult and varied in shape, with the left often being semilunar and right being pyramidal. Nervous supply of the adrenal glands is achieved by contributions from the splanchnic nerves of the celiac plexus. <br /> <br /> <br /> [[File:Dd.jpg|500px|thumb|right|Adult Adrenal Glands in situ]] <br /> ----<br /> <br /> ===Molecular mechanisms/factors/genes===<br /> ----<br /> <br /> ====Role of Adrenal Medulla in the Neonate and Adult====<br /> <br /> Understanding the biochemistry of catecholamines is necessary to see how the adrenal medulla is designed in the stages of embryology and how it is suited for life in the neonate and adult. <br /> <br /> The epinephrine and norepinephrine in the neonate and adult work by primarily changing the osmoregulatory state of vasculature in organs. With the exclusion of their neuromodulatory and neurotransmitter functions, epinephrine and norepinephrine are mainly tasked with the control of sympathetic and parasympathetic supplies. <br /> <br /> >Norepinephrine is a constrictor of peripheral vasculature by antagonising the action of surface receptors expressed on the endothelium of blood vessels, specifically Alpha-1 and Alpha-2 receptors, such that vascular resistance increases. <br /> <br /> >Epinephrine is both a vasoconstrictor and vasodilator, depending on what receptors it attaches to. As a non-selective adrenergic agonist, it acts on Alpha-1, Alpha-2, Beta-1, Beta-2 and Beta-3 receptors that are found throughout the body's tissues, yielding many different physiological responses.<br /> <br /> ====Genes and Transcription Factors Involved with the Adrenal Medulla's Development====<br /> <br /> Members of the SOX (SRY-Box) gene family have multiple key contributors to Neural Crest in the Adrenal Medulla.<br /> <br /> Mouse models have demonstrated that SOX-10 knock-outs (mice whose DNA has been engineered to not express SOX-10) do not have an adrenal medulla. There has also been suggestion that SOX-8,9 and 10 are all strongly related to the migratory patterning of neural crest cells to the developing adrenal glands.<br /> <br /> The TH gene (for Tyrosine Hydroxylase) encodes the aforementioned enzyme in the adrenal medulla and central nervous system. Tyrosine Hydroxylase is crucial in biochemical pathways and cascades for the synthesis of catecholamines and other CNS neurotransmitters. The conversion from L-Tyrosine to L-DOPA is dependent upon the catalytic action of Tyrosine Hydroxylase. From there, L-DOPA can make Dopamine and eventually Epinephrine and Norepinephrine as well. <br /> <br /> [[File:Catecholamine_Synthesis.jpg|500px|thumb|right|Cascade of Catecholamine Synthesis]]<br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2291442/<br /> https://www.ncbi.nlm.nih.gov/pubmed/19396395<br /> <br /> ===Abnormalities/abnormal development===<br /> ----<br /> ===Animal models===<br /> ----<br /> Animal models are an integral part of research in embryology. In particular due to the moral concerns regarding the use of humans in scientific research. As a result different animals are used as substitutes to simulate the same environments and hope to achieve results that would also be able to represent humans as well. Prenatal adrenal gland development has been described in a number of scientific reports dating from the 1900s to studies in more recent years. These involved a variety of animal models such as ox, sheep, swine and most commonly mice. <br /> <br /> <br /> There has been extensive research conducted into the adrenal chromaffin cells and their embryological developments. As explained above nueral crest cells are pluripotent meaning they are able to differentiate into multiple different cells. The neural crest cells give rise to chromaffin cells of the adrenal medulla.<br /> Ahonen suggested that some neural crest cells continue migration from the chain ganglia to the lateral sides of aorta, where they form the perirenal ganglia and adrenal medulla, and finally to the ventral side of the aorta to form the preaortic sympathetic tissue. However, that report only showed the several transverse sections of the fetal trunk for the a demonstration of the migration route of neural crest cells. In this study, using three dimensional reconstructed images, we aimed to observe how TH-labeled chromaffin cells penetrate into the adrenal anlage to form the adrenal medulla and whether the migration route of TH - positive cells from the adrenal connects the preaortic sympathetic ganglia <br /> (M.Yamato, R. Yanai, K. Arishima, 2004) <br /> <br /> Prenatal adrenal gland development has been described in numerous published reports covering a wide variety of species, including the ox (Katznelson, 1966; Wrobel and Suss, 1999), sheep (Davies, 1950; Wintour et al., 1975; Upadhyay and Zamboni, 1982; Naaman‐Reperant and Durand, 1997; Grino, 2004), swine (Sokolov et al., 2006) and mouse (Waring, 1935; Ikeda et al., 1994; Sass, 1996; Nyska and Maronpot, 1999; Bland et al., 2003; Val et al., 2007). Adrenal gland development also has been extensively described for humans as well (Kolliker, 1879; Minot, 1892; Zuckerkandl, 1912; Wieman, 1920; Ikeda et al., 1981; Langlois et al., 2002; Hanley and Arit, 2006).<br /> <br /> https://www.sciencedirect.com/science/article/pii/S0925477302004550<br /> http://dev.biologists.org/content/develop/126/13/2935.full.pdf<br /> <br /> ===Current research (labs)===<br /> ----<br /> The findings presented until now have focused on the mechanisms controlling migration along the dorsolateral path. In comparison, our understanding of the mechanisms controlling NCC migration along the ventral path are complicated by the fact that this population comprises multiple precursors that form different derivatives in distinct regions of the embryo. For example, ventrally migrating NCCs either stop within the sclerotome in close association with the neural tube to form neurons and glia of the sensory nervous system (i.e. the dorsal root ganglia [DRG]), while other NCCs continue to migrate further ventrally to form the autonomic nervous system (i.e. sympathetic ganglia and chromaffin cells of the adrenal gland)<br /> <br /> Adrenomedullary chromaffin cells are catecholamine (CA)-producing cells originating from trunk neural crest (NC) via sympathoadrenal progenitors (SAPs). We generated NC and SAPs from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) in vitro via BMP2/FGF2 exposure, ascertained by qPCR and immunoexpression of SOX10, ASCL1, TFAP2α, and PHOX2B, and by fluorescence-activated cell sorting selection for p75NTR and GD2, and confirmed their trunk-like HOX gene expression. We showed that continuing BMP4 and curtailing FGF2 in vitro, augmented with corticosteroid mimetic, induced these cells to upregulate the chromaffin cell-specific marker PNMT and other CA synthesis and storage markers, and we demonstrated noradrenaline and adrenaline by Faglu and high-performance liquid chromatography. We showed these human cells' SAP-like property of migration and differentiation into cells expressing chromaffin cell markers by implanting them into avian embryos in vivo and in chorio-allantoic membrane grafts. These cells have the potential for investigating differentiation of human chromaffin cells and for modeling diseases involving this cell type.<br /> <br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768882/<br /> <br /> ===Glossary===<br /> ----<br /> ===Reference list===</div>

Z5091101 https://embryology.med.unsw.edu.au/embryology/index.php?title=2018_Group_Project_1&diff=355707 2018 Group Project 1 2018-10-07T08:48:43Z

<p>Z5091101: /* History */</p> <hr /> <div>=The Contribution of Neural Crest Cells to the Adrenal Medulla=<br /> ----<br /> {{2018ANAT2341ProjectHeader}}<br /> <br /> <br /> ===Introduction===<br /> [[User:Z5014972|Z5014972]] ([[User talk:Z5014972|talk]]) 12:47, 14 August 2018 (AEST)z5014972 <br /> good review article https://link.springer.com/article/10.1007%2Fs12022-009-9070-6<br /> ----<br /> ===History===<br /> ----<br /> '''Describing the neural crest'''<br /> [[File:Wilhelm_His_History_Wilhelm.jpeg|left|230px|thumb|Wilhelm His]]<br /> The "neural crest" is a structure in the embryo and is the junction between the neural and epidermal ectoderm. The neural crest contributes a large number of cells of varying structure and function that directly or indirectly contribute to the development of tissues and organs within the body {{#pmid:19179766|PMID19179766}}. In 1868, the neural crest cells were first identified in a chick embryo as a collection of cells known as "Zwischenstrang" by Professor Wilhelm His {{#pmid:22820859|PMID22820859}}. Wilhelm His was among the first to provide an explanation for the mechanics governing the developing embryo as well as the physiology and the organs that the differing germinal regions would eventually give rise to. In 1878, the term neural ridge was used to describe this collection of cells but the term neural crest was later coined by Arthur Milnes Marshall in 1879 in a paper he worked on disseminating the knowledge from his research on the development of cranial nerves in chicken embryos. {{#pmid:19179766|PMID19179766}}.<br /> [[File:NC Location.jpg|left|450px|thumb|The neural crest]]<br /> <br /> '''1890s-1950s'''<br /> The neural crest is the point of origin for spinal/cranial ganglia and neurons. This theory received little criticism and was not contested much by other researchers prior to the 1890s. This is owing to the fact that the neural crest is quite closely related to the neural tube and thus this relationship makes sense. This discovery was made by His and Marshall, however, they found this out independently of one another.In the 1890s, Julia Platt, claimed that odontoblasts as well as the cartilages forming the facial and pharyngeal arch skeletons came from the ectoderm. This created much debate and was contested by many. <br /> <br /> This is because this theory completely contradicted the germ-layer theory, whereby skeletal tissues originate at the mesoderm and not the ectoderm. The controversies this finding created brought about a slowing down of research, as demonstrated by a gap of almost 40 years between the theory that skeletal tissues originating from the neural crest. Today, it is known that the neural crest does indeed play a role in the development of the skeleton in vertebrates, particularly, the cranial neural crest. Although these studies were occurring, the focus was still primarily on researching pigment cells and ganglia of the spine up until the 1950s, when Sven Hörstadius' major work on the neural crest was published, titled "The Neural Crest: Its properties and derivatives in the light of experimental research". This work focused on experimental data tracing the development of the cartilaginous skeleton derived from the neural crest {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1960s - 1970s'''<br /> In the 1960s, the migration patterns of neural crest cells were studied in avian embryos (birds). This was a shift from studying the embryos of amphibians. This was inspired by studies conducted in the 1960s on neural crest cells migrating from the brain and spinal cord, known as trunk and cranial neural crest cells {{#pmid:19179766|PMID19179766}}. The cranial neural crest eventually becomes the bones, cartilage and connective tissues forming the foundation of the face, ears and teeth. The trunk neural crest cells can either become melanocytes or can migrate into sclerotomes which are later contributors to the cartilage of the spine and the dorsal root ganglia {{#pmid:22820859|PMID22820859}}. The cells in the trunk neural crest that migrate vertically become the sympathetic ganglia, the nerves proximal to the aorta and the adrenal medulla <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. In the 1970s many detailed maps signifying the pathways of many of the neural crest cells appeared as well as an understanding that the environment in which the neural crest cells are found plays a major role in their final development as well as the occurrences of abnormalities in the fetus {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1980s - 21st century'''<br /> From the 1980s-1990s, the causative agent of organ transformation from one to another (homeotic patterning), as well as the Hox genes which regulate the axis of most symmetrical animal embryos were founded and studied. The neural crest, which previously was divided into the cranial and trunk regions, was now further divided into the vagal and sacral neural crest, the cardiac neural crest and the cephalic neural crest {{#pmid:19179766|PMID19179766}}. The vagal & sacral neural crest gives rise to the parasympathetic ganglia found in the gut. Without these ganglia, peristalsis, is not possible <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. [[File:Regions_of_NC_Cells.jpg|left|Neural crest regions|thumb]]The cardiac neural crest contributes to the valves, septa and major blood vessels of the heart, as well as connective tissues and cartilage{{#pmid:19179766|PMID19179766}}. This is important for the structure of the heart as well as its overall function, enabling it to move blood around the body efficiently as well as keep pulmonary and aortic circulation separated <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> <br /> <br /> Today, knowledge of the neural crest cells, their migration patterns, modes of differentiation, derivatives and apoptosis (cell death) are being studied extensively. This is being done on a comparative basis between different organisms, to add further evidence for evolution {{#pmid:19179766|PMID19179766}}. The neural crest is definitely forging a "crest" between the fields of developmental and evolutionary biology, as it is a structure '''shared exclusively by all vertebrates'''. Invertebrates do not derive their specialised cells from the neural crest as they do not have one, rather, they derive these from the endomesoderm {{#pmid:22230617|PMID22230617}}.<br /> <br /> '''Future directions'''<br /> <br /> Since its discovery by His, the neural crest field has made great progress, from studies performed on the structure, to analysis of the molecules and whether certain aspects of the neural crest are specific to a single species of organism, or to all vertebrates collectively. Future work on the cranial neural crest needs to be done as well as identifying and categorising the networks responsible for the proliferation and death of cells, as well as how the cells move and migrate, as well as the gene regulatory networks (GRNs) that regulate the synthesis of proteins. Advances in technology will undeniable lead us to more answers on the subject {{#pmid:22230617|PMID22230617}}.<br /> <br /> ===Embryonic origins===<br /> ----<br /> https://www.ncbi.nlm.nih.gov/books/NBK10065/<br /> <br /> ===Developmental time course===<br /> ----<br /> <br /> The adrenal gland has two distinct sections, the cortex and the medulla, both with different embryonic origins. The cortex accounts for 90% of the adrenal glands and arises from intermediate mesoderm. The medulla only accounts for 10% of the adult adrenal glands, however it has neural crest embryonic origin. The medulla consists of chromaffinoblast cells which are migrant neuroblast cells from the neural crest, therefore the adrenal medulla is a component of the sympathetic nervous system.{{#pmid:21175739|PMID21175739}} Neural crest cells replicate in week 7 and begin to differentiate in week 8, the cells then migrate to the developing adrenal gland in week 9 of development.{{#pmid:25255746|PMID25255746}}{{#pmid:18279781|PMID18279781}} The neural crest cells infiltrate the cortex and the chromaffin cells are scattered islands in the cortex.{{#pmid:23354096|PMID23354096}} Throughout development the cells will become more compact in the centre of the gland, during this period of development the adrenal gland is growing rapidly. The gland is abnormally large until the second trimester and the medulla is much thicker prenatally.{{#pmid:18279781|PMID18279781}}{{#pmid:21175739|PMID21175739}}<br /> <br /> ===Developmental/adult function===<br /> ----<br /> ===Tissue/organ structure===<br /> <br /> ====Normal Structure and Function of the Adrenal Medulla====<br /> <br /> The cells of the adrenal medulla are derived from the neural crest as opposed to the mesodermal origins of the cortex. The medulla contains secretory cells called chromaffin cells, due to the agents they produce when oxidised, such as chromate. These cells secrete epinephrine and norepinephrine in response to various substances such as acetylcholine.<br /> <br /> There are three types of cells in the adult adrenal medulla: <br /> 1) Epinephrine cells<br /> 2) Norepinephrine cells <br /> 3) Small granule-containing cells (SGCs)<br /> These cells also produce various other peptides such as substance P and neurotensin. The adrenal medulla also contains presynaptic sympathetic ganglion cells. <br /> <br /> <br /> ====Related Anatomy====<br /> <br /> The tissue and organ structure of the adrenal medulla should be understood with regard to its specialised function within the sympathetic nervous system. <br /> <br /> The medullary region of the adrenal glands is tasked with the endocrine secretions of adrenaline and nor-adrenaline in response to environmental stressors that are signalled for by the sympathetic nervous system. That is, the secretion of fight-or-flight response hormones in order to restrict vasculature to the trunk and increase vascular activity in the peripheral musculature.<br /> <br /> The adrenal glands are supplied by several branches of the great vessels in the abdominal cavity. The secreted catecholamines in the medulla are directly able to pass to the blood stream this way.<br /> <br /> These adrenal glands and their contents are retroperitoneal in the adult and varied in shape, with the left often being semilunar and right being pyramidal. Nervous supply of the adrenal glands is achieved by contributions from the splanchnic nerves of the celiac plexus. <br /> <br /> <br /> [[File:Dd.jpg|500px|thumb|right|Adult Adrenal Glands in situ]] <br /> ----<br /> <br /> ===Molecular mechanisms/factors/genes===<br /> ----<br /> <br /> ====Role of Adrenal Medulla in the Neonate and Adult====<br /> <br /> Understanding the biochemistry of catecholamines is necessary to see how the adrenal medulla is designed in the stages of embryology and how it is suited for life in the neonate and adult. <br /> <br /> The epinephrine and norepinephrine in the neonate and adult work by primarily changing the osmoregulatory state of vasculature in organs. With the exclusion of their neuromodulatory and neurotransmitter functions, epinephrine and norepinephrine are mainly tasked with the control of sympathetic and parasympathetic supplies. <br /> <br /> >Norepinephrine is a constrictor of peripheral vasculature by antagonising the action of surface receptors expressed on the endothelium of blood vessels, specifically Alpha-1 and Alpha-2 receptors, such that vascular resistance increases. <br /> <br /> >Epinephrine is both a vasoconstrictor and vasodilator, depending on what receptors it attaches to. As a non-selective adrenergic agonist, it acts on Alpha-1, Alpha-2, Beta-1, Beta-2 and Beta-3 receptors that are found throughout the body's tissues, yielding many different physiological responses.<br /> <br /> ====Genes and Transcription Factors Involved with the Adrenal Medulla's Development====<br /> <br /> Members of the SOX (SRY-Box) gene family have multiple key contributors to Neural Crest in the Adrenal Medulla.<br /> <br /> Mouse models have demonstrated that SOX-10 knock-outs (mice whose DNA has been engineered to not express SOX-10) do not have an adrenal medulla. There has also been suggestion that SOX-8,9 and 10 are all strongly related to the migratory patterning of neural crest cells to the developing adrenal glands.<br /> <br /> The TH gene (for Tyrosine Hydroxylase) encodes the aforementioned enzyme in the adrenal medulla and central nervous system. Tyrosine Hydroxylase is crucial in biochemical pathways and cascades for the synthesis of catecholamines and other CNS neurotransmitters. The conversion from L-Tyrosine to L-DOPA is dependent upon the catalytic action of Tyrosine Hydroxylase. From there, L-DOPA can make Dopamine and eventually Epinephrine and Norepinephrine as well. <br /> <br /> [[File:Catecholamine_Synthesis.jpg|500px|thumb|right|Cascade of Catecholamine Synthesis]]<br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2291442/<br /> https://www.ncbi.nlm.nih.gov/pubmed/19396395<br /> <br /> ===Abnormalities/abnormal development===<br /> ----<br /> ===Animal models===<br /> ----<br /> Animal models are an integral part of research in embryology. In particular due to the moral concerns regarding the use of humans in scientific research. As a result different animals are used as substitutes to simulate the same environments and hope to achieve results that would also be able to represent humans as well. Prenatal adrenal gland development has been described in a number of scientific reports dating from the 1900s to studies in more recent years. These involved a variety of animal models such as ox, sheep, swine and most commonly mice. <br /> <br /> <br /> There has been extensive research conducted into the adrenal chromaffin cells and their embryological developments. As explained above nueral crest cells are pluripotent meaning they are able to differentiate into multiple different cells. The neural crest cells give rise to chromaffin cells of the adrenal medulla.<br /> Ahonen suggested that some neural crest cells continue migration from the chain ganglia to the lateral sides of aorta, where they form the perirenal ganglia and adrenal medulla, and finally to the ventral side of the aorta to form the preaortic sympathetic tissue. However, that report only showed the several transverse sections of the fetal trunk for the a demonstration of the migration route of neural crest cells. In this study, using three dimensional reconstructed images, we aimed to observe how TH-labeled chromaffin cells penetrate into the adrenal anlage to form the adrenal medulla and whether the migration route of TH - positive cells from the adrenal connects the preaortic sympathetic ganglia <br /> (M.Yamato, R. Yanai, K. Arishima, 2004) <br /> <br /> Prenatal adrenal gland development has been described in numerous published reports covering a wide variety of species, including the ox (Katznelson, 1966; Wrobel and Suss, 1999), sheep (Davies, 1950; Wintour et al., 1975; Upadhyay and Zamboni, 1982; Naaman‐Reperant and Durand, 1997; Grino, 2004), swine (Sokolov et al., 2006) and mouse (Waring, 1935; Ikeda et al., 1994; Sass, 1996; Nyska and Maronpot, 1999; Bland et al., 2003; Val et al., 2007). Adrenal gland development also has been extensively described for humans as well (Kolliker, 1879; Minot, 1892; Zuckerkandl, 1912; Wieman, 1920; Ikeda et al., 1981; Langlois et al., 2002; Hanley and Arit, 2006).<br /> <br /> https://www.sciencedirect.com/science/article/pii/S0925477302004550<br /> http://dev.biologists.org/content/develop/126/13/2935.full.pdf<br /> <br /> ===Current research (labs)===<br /> ----<br /> The findings presented until now have focused on the mechanisms controlling migration along the dorsolateral path. In comparison, our understanding of the mechanisms controlling NCC migration along the ventral path are complicated by the fact that this population comprises multiple precursors that form different derivatives in distinct regions of the embryo. For example, ventrally migrating NCCs either stop within the sclerotome in close association with the neural tube to form neurons and glia of the sensory nervous system (i.e. the dorsal root ganglia [DRG]), while other NCCs continue to migrate further ventrally to form the autonomic nervous system (i.e. sympathetic ganglia and chromaffin cells of the adrenal gland)<br /> <br /> Adrenomedullary chromaffin cells are catecholamine (CA)-producing cells originating from trunk neural crest (NC) via sympathoadrenal progenitors (SAPs). We generated NC and SAPs from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) in vitro via BMP2/FGF2 exposure, ascertained by qPCR and immunoexpression of SOX10, ASCL1, TFAP2α, and PHOX2B, and by fluorescence-activated cell sorting selection for p75NTR and GD2, and confirmed their trunk-like HOX gene expression. We showed that continuing BMP4 and curtailing FGF2 in vitro, augmented with corticosteroid mimetic, induced these cells to upregulate the chromaffin cell-specific marker PNMT and other CA synthesis and storage markers, and we demonstrated noradrenaline and adrenaline by Faglu and high-performance liquid chromatography. We showed these human cells' SAP-like property of migration and differentiation into cells expressing chromaffin cell markers by implanting them into avian embryos in vivo and in chorio-allantoic membrane grafts. These cells have the potential for investigating differentiation of human chromaffin cells and for modeling diseases involving this cell type.<br /> <br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768882/<br /> <br /> ===Glossary===<br /> ----<br /> ===Reference list===</div>

Z5091101 https://embryology.med.unsw.edu.au/embryology/index.php?title=2018_Group_Project_1&diff=355705 2018 Group Project 1 2018-10-07T08:47:30Z

<p>Z5091101: /* History */</p> <hr /> <div>=The Contribution of Neural Crest Cells to the Adrenal Medulla=<br /> ----<br /> {{2018ANAT2341ProjectHeader}}<br /> <br /> <br /> ===Introduction===<br /> [[User:Z5014972|Z5014972]] ([[User talk:Z5014972|talk]]) 12:47, 14 August 2018 (AEST)z5014972 <br /> good review article https://link.springer.com/article/10.1007%2Fs12022-009-9070-6<br /> ----<br /> ===History===<br /> ----<br /> '''Describing the neural crest'''<br /> [[File:Wilhelm_His_History_Wilhelm.jpeg|left|230px|thumb|Wilhelm His]]<br /> The "neural crest" is a structure in the embryo and is the junction between the neural and epidermal ectoderm. The neural crest contributes a large number of cells of varying structure and function that directly or indirectly contribute to the development of tissues and organs within the body {{#pmid:19179766|PMID19179766}}. In 1868, the neural crest cells were first identified in a chick embryo as a collection of cells known as "Zwischenstrang" by Professor Wilhelm His {{#pmid:22820859|PMID22820859}}. Wilhelm His was among the first to provide an explanation for the mechanics governing the developing embryo as well as the physiology and the organs that the differing germinal regions would eventually give rise to. In 1878, the term neural ridge was used to describe this collection of cells but the term neural crest was later coined by Arthur Milnes Marshall in 1879 in a paper he worked on disseminating the knowledge from his research on the development of cranial nerves in chicken embryos. {{#pmid:19179766|PMID19179766}}.<br /> [[File:NC Location.jpg|right|450px|thumb|The neural crest]]<br /> <br /> '''1890s-1950s'''<br /> The neural crest is the point of origin for spinal/cranial ganglia and neurons. This theory received little criticism and was not contested much by other researchers prior to the 1890s. This is owing to the fact that the neural crest is quite closely related to the neural tube and thus this relationship makes sense. This discovery was made by His and Marshall, however, they found this out independently of one another.In the 1890s, Julia Platt, claimed that odontoblasts as well as the cartilages forming the facial and pharyngeal arch skeletons came from the ectoderm. This created much debate and was contested by many. <br /> <br /> This is because this theory completely contradicted the germ-layer theory, whereby skeletal tissues originate at the mesoderm and not the ectoderm. The controversies this finding created brought about a slowing down of research, as demonstrated by a gap of almost 40 years between the theory that skeletal tissues originating from the neural crest. Today, it is known that the neural crest does indeed play a role in the development of the skeleton in vertebrates, particularly, the cranial neural crest. Although these studies were occurring, the focus was still primarily on researching pigment cells and ganglia of the spine up until the 1950s, when Sven Hörstadius' major work on the neural crest was published, titled "The Neural Crest: Its properties and derivatives in the light of experimental research". This work focused on experimental data tracing the development of the cartilaginous skeleton derived from the neural crest {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1960s - 1970s'''<br /> In the 1960s, the migration patterns of neural crest cells were studied in avian embryos (birds). This was a shift from studying the embryos of amphibians. This was inspired by studies conducted in the 1960s on neural crest cells migrating from the brain and spinal cord, known as trunk and cranial neural crest cells {{#pmid:19179766|PMID19179766}}. The cranial neural crest eventually becomes the bones, cartilage and connective tissues forming the foundation of the face, ears and teeth. The trunk neural crest cells can either become melanocytes or can migrate into sclerotomes which are later contributors to the cartilage of the spine and the dorsal root ganglia {{#pmid:22820859|PMID22820859}}. The cells in the trunk neural crest that migrate vertically become the sympathetic ganglia, the nerves proximal to the aorta and the adrenal medulla <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. In the 1970s many detailed maps signifying the pathways of many of the neural crest cells appeared as well as an understanding that the environment in which the neural crest cells are found plays a major role in their final development as well as the occurrences of abnormalities in the fetus {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1980s - 21st century'''<br /> From the 1980s-1990s, the causative agent of organ transformation from one to another (homeotic patterning), as well as the Hox genes which regulate the axis of most symmetrical animal embryos were founded and studied. The neural crest, which previously was divided into the cranial and trunk regions, was now further divided into the vagal and sacral neural crest, the cardiac neural crest and the cephalic neural crest {{#pmid:19179766|PMID19179766}}. The vagal & sacral neural crest gives rise to the parasympathetic ganglia found in the gut. Without these ganglia, peristalsis, is not possible <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. The cardiac neural crest contributes to the valves, septa and major blood vessels of the heart, as well as connective tissues and cartilage{{#pmid:19179766|PMID19179766}}. This is important for the structure of the heart as well as its overall function, enabling it to move blood around the body efficiently as well as keep pulmonary and aortic circulation separated <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> <br /> [[File:Regions_of_NC_Cells.jpg|left|Neural crest regions|thumb]]<br /> Today, knowledge of the neural crest cells, their migration patterns, modes of differentiation, derivatives and apoptosis (cell death) are being studied extensively. This is being done on a comparative basis between different organisms, to add further evidence for evolution {{#pmid:19179766|PMID19179766}}. The neural crest is definitely forging a "crest" between the fields of developmental and evolutionary biology, as it is a structure '''shared exclusively by all vertebrates'''. Invertebrates do not derive their specialised cells from the neural crest as they do not have one, rather, they derive these from the endomesoderm {{#pmid:22230617|PMID22230617}}.<br /> <br /> '''Future directions'''<br /> <br /> Since its discovery by His, the neural crest field has made great progress, from studies performed on the structure, to analysis of the molecules and whether certain aspects of the neural crest are specific to a single species of organism, or to all vertebrates collectively. Future work on the cranial neural crest needs to be done as well as identifying and categorising the networks responsible for the proliferation and death of cells, as well as how the cells move and migrate, as well as the gene regulatory networks that regulate the synthesis of proteins. Advances in technology will undeniable lead us to more answers on the subject {{#pmid:22230617|PMID22230617}}.<br /> <br /> ===Embryonic origins===<br /> ----<br /> https://www.ncbi.nlm.nih.gov/books/NBK10065/<br /> <br /> ===Developmental time course===<br /> ----<br /> <br /> The adrenal gland has two distinct sections, the cortex and the medulla, both with different embryonic origins. The cortex accounts for 90% of the adrenal glands and arises from intermediate mesoderm. The medulla only accounts for 10% of the adult adrenal glands, however it has neural crest embryonic origin. The medulla consists of chromaffinoblast cells which are migrant neuroblast cells from the neural crest, therefore the adrenal medulla is a component of the sympathetic nervous system.{{#pmid:21175739|PMID21175739}} Neural crest cells replicate in week 7 and begin to differentiate in week 8, the cells then migrate to the developing adrenal gland in week 9 of development.{{#pmid:25255746|PMID25255746}}{{#pmid:18279781|PMID18279781}} The neural crest cells infiltrate the cortex and the chromaffin cells are scattered islands in the cortex.{{#pmid:23354096|PMID23354096}} Throughout development the cells will become more compact in the centre of the gland, during this period of development the adrenal gland is growing rapidly. The gland is abnormally large until the second trimester and the medulla is much thicker prenatally.{{#pmid:18279781|PMID18279781}}{{#pmid:21175739|PMID21175739}}<br /> <br /> ===Developmental/adult function===<br /> ----<br /> ===Tissue/organ structure===<br /> <br /> ====Normal Structure and Function of the Adrenal Medulla====<br /> <br /> The cells of the adrenal medulla are derived from the neural crest as opposed to the mesodermal origins of the cortex. The medulla contains secretory cells called chromaffin cells, due to the agents they produce when oxidised, such as chromate. These cells secrete epinephrine and norepinephrine in response to various substances such as acetylcholine.<br /> <br /> There are three types of cells in the adult adrenal medulla: <br /> 1) Epinephrine cells<br /> 2) Norepinephrine cells <br /> 3) Small granule-containing cells (SGCs)<br /> These cells also produce various other peptides such as substance P and neurotensin. The adrenal medulla also contains presynaptic sympathetic ganglion cells. <br /> <br /> <br /> ====Related Anatomy====<br /> <br /> The tissue and organ structure of the adrenal medulla should be understood with regard to its specialised function within the sympathetic nervous system. <br /> <br /> The medullary region of the adrenal glands is tasked with the endocrine secretions of adrenaline and nor-adrenaline in response to environmental stressors that are signalled for by the sympathetic nervous system. That is, the secretion of fight-or-flight response hormones in order to restrict vasculature to the trunk and increase vascular activity in the peripheral musculature.<br /> <br /> The adrenal glands are supplied by several branches of the great vessels in the abdominal cavity. The secreted catecholamines in the medulla are directly able to pass to the blood stream this way.<br /> <br /> These adrenal glands and their contents are retroperitoneal in the adult and varied in shape, with the left often being semilunar and right being pyramidal. Nervous supply of the adrenal glands is achieved by contributions from the splanchnic nerves of the celiac plexus. <br /> <br /> <br /> [[File:Dd.jpg|500px|thumb|right|Adult Adrenal Glands in situ]] <br /> ----<br /> <br /> ===Molecular mechanisms/factors/genes===<br /> ----<br /> <br /> ====Role of Adrenal Medulla in the Neonate and Adult====<br /> <br /> Understanding the biochemistry of catecholamines is necessary to see how the adrenal medulla is designed in the stages of embryology and how it is suited for life in the neonate and adult. <br /> <br /> The epinephrine and norepinephrine in the neonate and adult work by primarily changing the osmoregulatory state of vasculature in organs. With the exclusion of their neuromodulatory and neurotransmitter functions, epinephrine and norepinephrine are mainly tasked with the control of sympathetic and parasympathetic supplies. <br /> <br /> >Norepinephrine is a constrictor of peripheral vasculature by antagonising the action of surface receptors expressed on the endothelium of blood vessels, specifically Alpha-1 and Alpha-2 receptors, such that vascular resistance increases. <br /> <br /> >Epinephrine is both a vasoconstrictor and vasodilator, depending on what receptors it attaches to. As a non-selective adrenergic agonist, it acts on Alpha-1, Alpha-2, Beta-1, Beta-2 and Beta-3 receptors that are found throughout the body's tissues, yielding many different physiological responses.<br /> <br /> ====Genes and Transcription Factors Involved with the Adrenal Medulla's Development====<br /> <br /> Members of the SOX (SRY-Box) gene family have multiple key contributors to Neural Crest in the Adrenal Medulla.<br /> <br /> Mouse models have demonstrated that SOX-10 knock-outs (mice whose DNA has been engineered to not express SOX-10) do not have an adrenal medulla. There has also been suggestion that SOX-8,9 and 10 are all strongly related to the migratory patterning of neural crest cells to the developing adrenal glands.<br /> <br /> The TH gene (for Tyrosine Hydroxylase) encodes the aforementioned enzyme in the adrenal medulla and central nervous system. Tyrosine Hydroxylase is crucial in biochemical pathways and cascades for the synthesis of catecholamines and other CNS neurotransmitters. The conversion from L-Tyrosine to L-DOPA is dependent upon the catalytic action of Tyrosine Hydroxylase. From there, L-DOPA can make Dopamine and eventually Epinephrine and Norepinephrine as well. <br /> <br /> [[File:Catecholamine_Synthesis.jpg|500px|thumb|right|Cascade of Catecholamine Synthesis]]<br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2291442/<br /> https://www.ncbi.nlm.nih.gov/pubmed/19396395<br /> <br /> ===Abnormalities/abnormal development===<br /> ----<br /> ===Animal models===<br /> ----<br /> Animal models are an integral part of research in embryology. In particular due to the moral concerns regarding the use of humans in scientific research. As a result different animals are used as substitutes to simulate the same environments and hope to achieve results that would also be able to represent humans as well. Prenatal adrenal gland development has been described in a number of scientific reports dating from the 1900s to studies in more recent years. These involved a variety of animal models such as ox, sheep, swine and most commonly mice. <br /> <br /> <br /> There has been extensive research conducted into the adrenal chromaffin cells and their embryological developments. As explained above nueral crest cells are pluripotent meaning they are able to differentiate into multiple different cells. The neural crest cells give rise to chromaffin cells of the adrenal medulla.<br /> Ahonen suggested that some neural crest cells continue migration from the chain ganglia to the lateral sides of aorta, where they form the perirenal ganglia and adrenal medulla, and finally to the ventral side of the aorta to form the preaortic sympathetic tissue. However, that report only showed the several transverse sections of the fetal trunk for the a demonstration of the migration route of neural crest cells. In this study, using three dimensional reconstructed images, we aimed to observe how TH-labeled chromaffin cells penetrate into the adrenal anlage to form the adrenal medulla and whether the migration route of TH - positive cells from the adrenal connects the preaortic sympathetic ganglia <br /> (M.Yamato, R. Yanai, K. Arishima, 2004) <br /> <br /> Prenatal adrenal gland development has been described in numerous published reports covering a wide variety of species, including the ox (Katznelson, 1966; Wrobel and Suss, 1999), sheep (Davies, 1950; Wintour et al., 1975; Upadhyay and Zamboni, 1982; Naaman‐Reperant and Durand, 1997; Grino, 2004), swine (Sokolov et al., 2006) and mouse (Waring, 1935; Ikeda et al., 1994; Sass, 1996; Nyska and Maronpot, 1999; Bland et al., 2003; Val et al., 2007). Adrenal gland development also has been extensively described for humans as well (Kolliker, 1879; Minot, 1892; Zuckerkandl, 1912; Wieman, 1920; Ikeda et al., 1981; Langlois et al., 2002; Hanley and Arit, 2006).<br /> <br /> https://www.sciencedirect.com/science/article/pii/S0925477302004550<br /> http://dev.biologists.org/content/develop/126/13/2935.full.pdf<br /> <br /> ===Current research (labs)===<br /> ----<br /> The findings presented until now have focused on the mechanisms controlling migration along the dorsolateral path. In comparison, our understanding of the mechanisms controlling NCC migration along the ventral path are complicated by the fact that this population comprises multiple precursors that form different derivatives in distinct regions of the embryo. For example, ventrally migrating NCCs either stop within the sclerotome in close association with the neural tube to form neurons and glia of the sensory nervous system (i.e. the dorsal root ganglia [DRG]), while other NCCs continue to migrate further ventrally to form the autonomic nervous system (i.e. sympathetic ganglia and chromaffin cells of the adrenal gland)<br /> <br /> Adrenomedullary chromaffin cells are catecholamine (CA)-producing cells originating from trunk neural crest (NC) via sympathoadrenal progenitors (SAPs). We generated NC and SAPs from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) in vitro via BMP2/FGF2 exposure, ascertained by qPCR and immunoexpression of SOX10, ASCL1, TFAP2α, and PHOX2B, and by fluorescence-activated cell sorting selection for p75NTR and GD2, and confirmed their trunk-like HOX gene expression. We showed that continuing BMP4 and curtailing FGF2 in vitro, augmented with corticosteroid mimetic, induced these cells to upregulate the chromaffin cell-specific marker PNMT and other CA synthesis and storage markers, and we demonstrated noradrenaline and adrenaline by Faglu and high-performance liquid chromatography. We showed these human cells' SAP-like property of migration and differentiation into cells expressing chromaffin cell markers by implanting them into avian embryos in vivo and in chorio-allantoic membrane grafts. These cells have the potential for investigating differentiation of human chromaffin cells and for modeling diseases involving this cell type.<br /> <br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768882/<br /> <br /> ===Glossary===<br /> ----<br /> ===Reference list===</div>

Z5091101 https://embryology.med.unsw.edu.au/embryology/index.php?title=2018_Group_Project_1&diff=355703 2018 Group Project 1 2018-10-07T08:46:59Z

<p>Z5091101: /* History */</p> <hr /> <div>=The Contribution of Neural Crest Cells to the Adrenal Medulla=<br /> ----<br /> {{2018ANAT2341ProjectHeader}}<br /> <br /> <br /> ===Introduction===<br /> [[User:Z5014972|Z5014972]] ([[User talk:Z5014972|talk]]) 12:47, 14 August 2018 (AEST)z5014972 <br /> good review article https://link.springer.com/article/10.1007%2Fs12022-009-9070-6<br /> ----<br /> ===History===<br /> ----<br /> '''Describing the neural crest'''<br /> [[File:Wilhelm_His_History_Wilhelm.jpeg|left|230px|thumb|Wilhelm His]]<br /> The "neural crest" is a structure in the embryo and is the junction between the neural and epidermal ectoderm. The neural crest contributes a large number of cells of varying structure and function that directly or indirectly contribute to the development of tissues and organs within the body {{#pmid:19179766|PMID19179766}}. In 1868, the neural crest cells were first identified in a chick embryo as a collection of cells known as "Zwischenstrang" by Professor Wilhelm His {{#pmid:22820859|PMID22820859}}. Wilhelm His was among the first to provide an explanation for the mechanics governing the developing embryo as well as the physiology and the organs that the differing germinal regions would eventually give rise to. In 1878, the term neural ridge was used to describe this collection of cells but the term neural crest was later coined by Arthur Milnes Marshall in 1879 in a paper he worked on disseminating the knowledge from his research on the development of cranial nerves in chicken embryos. {{#pmid:19179766|PMID19179766}}.<br /> [[File:NC Location.jpg|left|500px|thumb|The neural crest]]<br /> <br /> '''1890s-1950s'''<br /> The neural crest is the point of origin for spinal/cranial ganglia and neurons. This theory received little criticism and was not contested much by other researchers prior to the 1890s. This is owing to the fact that the neural crest is quite closely related to the neural tube and thus this relationship makes sense. This discovery was made by His and Marshall, however, they found this out independently of one another.In the 1890s, Julia Platt, claimed that odontoblasts as well as the cartilages forming the facial and pharyngeal arch skeletons came from the ectoderm. This created much debate and was contested by many. <br /> <br /> This is because this theory completely contradicted the germ-layer theory, whereby skeletal tissues originate at the mesoderm and not the ectoderm. The controversies this finding created brought about a slowing down of research, as demonstrated by a gap of almost 40 years between the theory that skeletal tissues originating from the neural crest. Today, it is known that the neural crest does indeed play a role in the development of the skeleton in vertebrates, particularly, the cranial neural crest. Although these studies were occurring, the focus was still primarily on researching pigment cells and ganglia of the spine up until the 1950s, when Sven Hörstadius' major work on the neural crest was published, titled "The Neural Crest: Its properties and derivatives in the light of experimental research". This work focused on experimental data tracing the development of the cartilaginous skeleton derived from the neural crest {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1960s - 1970s'''<br /> In the 1960s, the migration patterns of neural crest cells were studied in avian embryos (birds). This was a shift from studying the embryos of amphibians. This was inspired by studies conducted in the 1960s on neural crest cells migrating from the brain and spinal cord, known as trunk and cranial neural crest cells {{#pmid:19179766|PMID19179766}}. The cranial neural crest eventually becomes the bones, cartilage and connective tissues forming the foundation of the face, ears and teeth. The trunk neural crest cells can either become melanocytes or can migrate into sclerotomes which are later contributors to the cartilage of the spine and the dorsal root ganglia {{#pmid:22820859|PMID22820859}}. The cells in the trunk neural crest that migrate vertically become the sympathetic ganglia, the nerves proximal to the aorta and the adrenal medulla <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. In the 1970s many detailed maps signifying the pathways of many of the neural crest cells appeared as well as an understanding that the environment in which the neural crest cells are found plays a major role in their final development as well as the occurrences of abnormalities in the fetus {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1980s - 21st century'''<br /> From the 1980s-1990s, the causative agent of organ transformation from one to another (homeotic patterning), as well as the Hox genes which regulate the axis of most symmetrical animal embryos were founded and studied. The neural crest, which previously was divided into the cranial and trunk regions, was now further divided into the vagal and sacral neural crest, the cardiac neural crest and the cephalic neural crest {{#pmid:19179766|PMID19179766}}. The vagal & sacral neural crest gives rise to the parasympathetic ganglia found in the gut. Without these ganglia, peristalsis, is not possible <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. The cardiac neural crest contributes to the valves, septa and major blood vessels of the heart, as well as connective tissues and cartilage{{#pmid:19179766|PMID19179766}}. This is important for the structure of the heart as well as its overall function, enabling it to move blood around the body efficiently as well as keep pulmonary and aortic circulation separated <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> <br /> [[File:Regions_of_NC_Cells.jpg|left|Neural crest regions|thumb]]<br /> Today, knowledge of the neural crest cells, their migration patterns, modes of differentiation, derivatives and apoptosis (cell death) are being studied extensively. This is being done on a comparative basis between different organisms, to add further evidence for evolution {{#pmid:19179766|PMID19179766}}. The neural crest is definitely forging a "crest" between the fields of developmental and evolutionary biology, as it is a structure '''shared exclusively by all vertebrates'''. Invertebrates do not derive their specialised cells from the neural crest as they do not have one, rather, they derive these from the endomesoderm {{#pmid:22230617|PMID22230617}}.<br /> <br /> '''Future directions'''<br /> <br /> Since its discovery by His, the neural crest field has made great progress, from studies performed on the structure, to analysis of the molecules and whether certain aspects of the neural crest are specific to a single species of organism, or to all vertebrates collectively. Future work on the cranial neural crest needs to be done as well as identifying and categorising the networks responsible for the proliferation and death of cells, as well as how the cells move and migrate, as well as the gene regulatory networks that regulate the synthesis of proteins. Advances in technology will undeniable lead us to more answers on the subject {{#pmid:22230617|PMID22230617}}.<br /> <br /> ===Embryonic origins===<br /> ----<br /> https://www.ncbi.nlm.nih.gov/books/NBK10065/<br /> <br /> ===Developmental time course===<br /> ----<br /> <br /> The adrenal gland has two distinct sections, the cortex and the medulla, both with different embryonic origins. The cortex accounts for 90% of the adrenal glands and arises from intermediate mesoderm. The medulla only accounts for 10% of the adult adrenal glands, however it has neural crest embryonic origin. The medulla consists of chromaffinoblast cells which are migrant neuroblast cells from the neural crest, therefore the adrenal medulla is a component of the sympathetic nervous system.{{#pmid:21175739|PMID21175739}} Neural crest cells replicate in week 7 and begin to differentiate in week 8, the cells then migrate to the developing adrenal gland in week 9 of development.{{#pmid:25255746|PMID25255746}}{{#pmid:18279781|PMID18279781}} The neural crest cells infiltrate the cortex and the chromaffin cells are scattered islands in the cortex.{{#pmid:23354096|PMID23354096}} Throughout development the cells will become more compact in the centre of the gland, during this period of development the adrenal gland is growing rapidly. The gland is abnormally large until the second trimester and the medulla is much thicker prenatally.{{#pmid:18279781|PMID18279781}}{{#pmid:21175739|PMID21175739}}<br /> <br /> ===Developmental/adult function===<br /> ----<br /> ===Tissue/organ structure===<br /> <br /> ====Normal Structure and Function of the Adrenal Medulla====<br /> <br /> The cells of the adrenal medulla are derived from the neural crest as opposed to the mesodermal origins of the cortex. The medulla contains secretory cells called chromaffin cells, due to the agents they produce when oxidised, such as chromate. These cells secrete epinephrine and norepinephrine in response to various substances such as acetylcholine.<br /> <br /> There are three types of cells in the adult adrenal medulla: <br /> 1) Epinephrine cells<br /> 2) Norepinephrine cells <br /> 3) Small granule-containing cells (SGCs)<br /> These cells also produce various other peptides such as substance P and neurotensin. The adrenal medulla also contains presynaptic sympathetic ganglion cells. <br /> <br /> <br /> ====Related Anatomy====<br /> <br /> The tissue and organ structure of the adrenal medulla should be understood with regard to its specialised function within the sympathetic nervous system. <br /> <br /> The medullary region of the adrenal glands is tasked with the endocrine secretions of adrenaline and nor-adrenaline in response to environmental stressors that are signalled for by the sympathetic nervous system. That is, the secretion of fight-or-flight response hormones in order to restrict vasculature to the trunk and increase vascular activity in the peripheral musculature.<br /> <br /> The adrenal glands are supplied by several branches of the great vessels in the abdominal cavity. The secreted catecholamines in the medulla are directly able to pass to the blood stream this way.<br /> <br /> These adrenal glands and their contents are retroperitoneal in the adult and varied in shape, with the left often being semilunar and right being pyramidal. Nervous supply of the adrenal glands is achieved by contributions from the splanchnic nerves of the celiac plexus. <br /> <br /> <br /> [[File:Dd.jpg|500px|thumb|right|Adult Adrenal Glands in situ]] <br /> ----<br /> <br /> ===Molecular mechanisms/factors/genes===<br /> ----<br /> <br /> ====Role of Adrenal Medulla in the Neonate and Adult====<br /> <br /> Understanding the biochemistry of catecholamines is necessary to see how the adrenal medulla is designed in the stages of embryology and how it is suited for life in the neonate and adult. <br /> <br /> The epinephrine and norepinephrine in the neonate and adult work by primarily changing the osmoregulatory state of vasculature in organs. With the exclusion of their neuromodulatory and neurotransmitter functions, epinephrine and norepinephrine are mainly tasked with the control of sympathetic and parasympathetic supplies. <br /> <br /> >Norepinephrine is a constrictor of peripheral vasculature by antagonising the action of surface receptors expressed on the endothelium of blood vessels, specifically Alpha-1 and Alpha-2 receptors, such that vascular resistance increases. <br /> <br /> >Epinephrine is both a vasoconstrictor and vasodilator, depending on what receptors it attaches to. As a non-selective adrenergic agonist, it acts on Alpha-1, Alpha-2, Beta-1, Beta-2 and Beta-3 receptors that are found throughout the body's tissues, yielding many different physiological responses.<br /> <br /> ====Genes and Transcription Factors Involved with the Adrenal Medulla's Development====<br /> <br /> Members of the SOX (SRY-Box) gene family have multiple key contributors to Neural Crest in the Adrenal Medulla.<br /> <br /> Mouse models have demonstrated that SOX-10 knock-outs (mice whose DNA has been engineered to not express SOX-10) do not have an adrenal medulla. There has also been suggestion that SOX-8,9 and 10 are all strongly related to the migratory patterning of neural crest cells to the developing adrenal glands.<br /> <br /> The TH gene (for Tyrosine Hydroxylase) encodes the aforementioned enzyme in the adrenal medulla and central nervous system. Tyrosine Hydroxylase is crucial in biochemical pathways and cascades for the synthesis of catecholamines and other CNS neurotransmitters. The conversion from L-Tyrosine to L-DOPA is dependent upon the catalytic action of Tyrosine Hydroxylase. From there, L-DOPA can make Dopamine and eventually Epinephrine and Norepinephrine as well. <br /> <br /> [[File:Catecholamine_Synthesis.jpg|500px|thumb|right|Cascade of Catecholamine Synthesis]]<br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2291442/<br /> https://www.ncbi.nlm.nih.gov/pubmed/19396395<br /> <br /> ===Abnormalities/abnormal development===<br /> ----<br /> ===Animal models===<br /> ----<br /> Animal models are an integral part of research in embryology. In particular due to the moral concerns regarding the use of humans in scientific research. As a result different animals are used as substitutes to simulate the same environments and hope to achieve results that would also be able to represent humans as well. Prenatal adrenal gland development has been described in a number of scientific reports dating from the 1900s to studies in more recent years. These involved a variety of animal models such as ox, sheep, swine and most commonly mice. <br /> <br /> <br /> There has been extensive research conducted into the adrenal chromaffin cells and their embryological developments. As explained above nueral crest cells are pluripotent meaning they are able to differentiate into multiple different cells. The neural crest cells give rise to chromaffin cells of the adrenal medulla.<br /> Ahonen suggested that some neural crest cells continue migration from the chain ganglia to the lateral sides of aorta, where they form the perirenal ganglia and adrenal medulla, and finally to the ventral side of the aorta to form the preaortic sympathetic tissue. However, that report only showed the several transverse sections of the fetal trunk for the a demonstration of the migration route of neural crest cells. In this study, using three dimensional reconstructed images, we aimed to observe how TH-labeled chromaffin cells penetrate into the adrenal anlage to form the adrenal medulla and whether the migration route of TH - positive cells from the adrenal connects the preaortic sympathetic ganglia <br /> (M.Yamato, R. Yanai, K. Arishima, 2004) <br /> <br /> Prenatal adrenal gland development has been described in numerous published reports covering a wide variety of species, including the ox (Katznelson, 1966; Wrobel and Suss, 1999), sheep (Davies, 1950; Wintour et al., 1975; Upadhyay and Zamboni, 1982; Naaman‐Reperant and Durand, 1997; Grino, 2004), swine (Sokolov et al., 2006) and mouse (Waring, 1935; Ikeda et al., 1994; Sass, 1996; Nyska and Maronpot, 1999; Bland et al., 2003; Val et al., 2007). Adrenal gland development also has been extensively described for humans as well (Kolliker, 1879; Minot, 1892; Zuckerkandl, 1912; Wieman, 1920; Ikeda et al., 1981; Langlois et al., 2002; Hanley and Arit, 2006).<br /> <br /> https://www.sciencedirect.com/science/article/pii/S0925477302004550<br /> http://dev.biologists.org/content/develop/126/13/2935.full.pdf<br /> <br /> ===Current research (labs)===<br /> ----<br /> The findings presented until now have focused on the mechanisms controlling migration along the dorsolateral path. In comparison, our understanding of the mechanisms controlling NCC migration along the ventral path are complicated by the fact that this population comprises multiple precursors that form different derivatives in distinct regions of the embryo. For example, ventrally migrating NCCs either stop within the sclerotome in close association with the neural tube to form neurons and glia of the sensory nervous system (i.e. the dorsal root ganglia [DRG]), while other NCCs continue to migrate further ventrally to form the autonomic nervous system (i.e. sympathetic ganglia and chromaffin cells of the adrenal gland)<br /> <br /> Adrenomedullary chromaffin cells are catecholamine (CA)-producing cells originating from trunk neural crest (NC) via sympathoadrenal progenitors (SAPs). We generated NC and SAPs from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) in vitro via BMP2/FGF2 exposure, ascertained by qPCR and immunoexpression of SOX10, ASCL1, TFAP2α, and PHOX2B, and by fluorescence-activated cell sorting selection for p75NTR and GD2, and confirmed their trunk-like HOX gene expression. We showed that continuing BMP4 and curtailing FGF2 in vitro, augmented with corticosteroid mimetic, induced these cells to upregulate the chromaffin cell-specific marker PNMT and other CA synthesis and storage markers, and we demonstrated noradrenaline and adrenaline by Faglu and high-performance liquid chromatography. We showed these human cells' SAP-like property of migration and differentiation into cells expressing chromaffin cell markers by implanting them into avian embryos in vivo and in chorio-allantoic membrane grafts. These cells have the potential for investigating differentiation of human chromaffin cells and for modeling diseases involving this cell type.<br /> <br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768882/<br /> <br /> ===Glossary===<br /> ----<br /> ===Reference list===</div>

Z5091101 https://embryology.med.unsw.edu.au/embryology/index.php?title=2018_Group_Project_1&diff=355701 2018 Group Project 1 2018-10-07T08:44:12Z

<p>Z5091101: /* History */</p> <hr /> <div>=The Contribution of Neural Crest Cells to the Adrenal Medulla=<br /> ----<br /> {{2018ANAT2341ProjectHeader}}<br /> <br /> <br /> ===Introduction===<br /> [[User:Z5014972|Z5014972]] ([[User talk:Z5014972|talk]]) 12:47, 14 August 2018 (AEST)z5014972 <br /> good review article https://link.springer.com/article/10.1007%2Fs12022-009-9070-6<br /> ----<br /> ===History===<br /> ----<br /> '''Describing the neural crest'''<br /> [[File:Wilhelm_His_History_Wilhelm.jpeg|left|230px|thumb|Wilhelm His]]<br /> The "neural crest" is a structure in the embryo and is the junction between the neural and epidermal ectoderm. The neural crest contributes a large number of cells of varying structure and function that directly or indirectly contribute to the development of tissues and organs within the body {{#pmid:19179766|PMID19179766}}. In 1868, the neural crest cells were first identified in a chick embryo as a collection of cells known as "Zwischenstrang" by Professor Wilhelm His {{#pmid:22820859|PMID22820859}}. Wilhelm His was among the first to provide an explanation for the mechanics governing the developing embryo as well as the physiology and the organs that the differing germinal regions would eventually give rise to. In 1878, the term neural ridge was used to describe this collection of cells but the term neural crest was later coined by Arthur Milnes Marshall in 1879 in a paper he worked on disseminating the knowledge from his research on the development of cranial nerves in chicken embryos. {{#pmid:19179766|PMID19179766}}.<br /> [[File:NC Location.jpg|left|500px|thumb|The neural crest]]<br /> <br /> '''1890s-1950s'''<br /> The neural crest is the point of origin for spinal/cranial ganglia and neurons. This theory received little criticism and was not contested much by other researchers prior to the 1890s. This is owing to the fact that the neural crest is quite closely related to the neural tube and thus this relationship makes sense. This discovery was made by His and Marshall, however, they found this out independently of one another.In the 1890s, Julia Platt, claimed that odontoblasts as well as the cartilages forming the facial and pharyngeal arch skeletons came from the ectoderm. This created much debate and was contested by many. <br /> <br /> This is because this theory completely contradicted the germ-layer theory, whereby skeletal tissues originate at the mesoderm and not the ectoderm. The controversies this finding created brought about a slowing down of research, as demonstrated by a gap of almost 40 years between the theory that skeletal tissues originating from the neural crest. Today, it is known that the neural crest does indeed play a role in the development of the skeleton in vertebrates, particularly, the cranial neural crest. Although these studies were occurring, the focus was still primarily on researching pigment cells and ganglia of the spine up until the 1950s, when Sven Hörstadius' major work on the neural crest was published, titled "The Neural Crest: Its properties and derivatives in the light of experimental research". This work focused on experimental data tracing the development of the cartilaginous skeleton derived from the neural crest {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1960s - 1970s'''<br /> In the 1960s, the migration patterns of neural crest cells were studied in avian embryos (birds). This was a shift from studying the embryos of amphibians. This was inspired by studies conducted in the 1960s on neural crest cells migrating from the brain and spinal cord, known as trunk and cranial neural crest cells {{#pmid:19179766|PMID19179766}}. The cranial neural crest eventually becomes the bones, cartilage and connective tissues forming the foundation of the face, ears and teeth. The trunk neural crest cells can either become melanocytes or can migrate into sclerotomes which are later contributors to the cartilage of the spine and the dorsal root ganglia {{#pmid:22820859|PMID22820859}}. The cells in the trunk neural crest that migrate vertically become the sympathetic ganglia, the nerves proximal to the aorta and the adrenal medulla <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. In the 1970s many detailed maps signifying the pathways of many of the neural crest cells appeared as well as an understanding that the environment in which the neural crest cells are found plays a major role in their final development as well as the occurrences of abnormalities in the fetus {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1980s - 21st century'''<br /> From the 1980s-1990s, the causative agent of organ transformation from one to another (homeotic patterning), as well as the Hox genes which regulate the axis of most symmetrical animal embryos were founded and studied. The neural crest, which previously was divided into the cranial and trunk regions, was now further divided into the vagal and sacral neural crest, the cardiac neural crest and the cephalic neural crest {{#pmid:19179766|PMID19179766}}. The vagal & sacral neural crest gives rise to the parasympathetic ganglia found in the gut. Without these ganglia, peristalsis, is not possible <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. The cardiac neural crest contributes to the valves, septa and major blood vessels of the heart, as well as connective tissues and cartilage{{#pmid:19179766|PMID19179766}}. This is important for the structure of the heart as well as its overall function, enabling it to move blood around the body efficiently as well as keep pulmonary and aortic circulation separated <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> <br /> [[File:Regions_of_NC_Cells.jpg|left|Neural crest regions|thumb]]<br /> Today, knowledge of the neural crest cells, their migration patterns, modes of differentiation, derivatives and apoptosis (cell death) are being studied extensively. This is being done on a comparative basis between different organisms, to add further evidence for evolution {{#pmid:19179766|PMID19179766}}. The neural crest is definitely forging a "crest" between the fields of developmental and evolutionary biology, as it is a structure '''shared exclusively by all vertebrates'''. Invertebrates do not derive their specialised cells from the neural crest as they do not have one, rather, they derive these from the endomesoderm {{#pmid:22230617|PMID22230617}}.<br /> <br /> '''Future directions'''<br /> Since its discovery by His, the neural crest field has made great progress, from studies performed on the structure, to analysis of the molecules and whether certain aspects of the neural crest are specific to a single species of organism, or to all vertebrates collectively. Future work on the cranial neural crest needs to be done as well as identifying and categorising the networks responsible for the proliferation and death of cells, as well as how the cells move and migrate, as well as the gene regulatory networks that regulate the synthesis of proteins. Advances in technology will undeniable lead us to more answers on the subject {{#pmid:22230617|PMID22230617}}.<br /> <br /> ===Embryonic origins===<br /> ----<br /> https://www.ncbi.nlm.nih.gov/books/NBK10065/<br /> <br /> ===Developmental time course===<br /> ----<br /> <br /> The adrenal gland has two distinct sections, the cortex and the medulla, both with different embryonic origins. The cortex accounts for 90% of the adrenal glands and arises from intermediate mesoderm. The medulla only accounts for 10% of the adult adrenal glands, however it has neural crest embryonic origin. The medulla consists of chromaffinoblast cells which are migrant neuroblast cells from the neural crest, therefore the adrenal medulla is a component of the sympathetic nervous system.{{#pmid:21175739|PMID21175739}} Neural crest cells replicate in week 7 and begin to differentiate in week 8, the cells then migrate to the developing adrenal gland in week 9 of development.{{#pmid:25255746|PMID25255746}}{{#pmid:18279781|PMID18279781}} The neural crest cells infiltrate the cortex and the chromaffin cells are scattered islands in the cortex.{{#pmid:23354096|PMID23354096}} Throughout development the cells will become more compact in the centre of the gland, during this period of development the adrenal gland is growing rapidly. The gland is abnormally large until the second trimester and the medulla is much thicker prenatally.{{#pmid:18279781|PMID18279781}}{{#pmid:21175739|PMID21175739}}<br /> <br /> ===Developmental/adult function===<br /> ----<br /> ===Tissue/organ structure===<br /> <br /> ====Normal Structure and Function of the Adrenal Medulla====<br /> <br /> The cells of the adrenal medulla are derived from the neural crest as opposed to the mesodermal origins of the cortex. The medulla contains secretory cells called chromaffin cells, due to the agents they produce when oxidised, such as chromate. These cells secrete epinephrine and norepinephrine in response to various substances such as acetylcholine.<br /> <br /> There are three types of cells in the adult adrenal medulla: <br /> 1) Epinephrine cells<br /> 2) Norepinephrine cells <br /> 3) Small granule-containing cells (SGCs)<br /> These cells also produce various other peptides such as substance P and neurotensin. The adrenal medulla also contains presynaptic sympathetic ganglion cells. <br /> <br /> <br /> ====Related Anatomy====<br /> <br /> The tissue and organ structure of the adrenal medulla should be understood with regard to its specialised function within the sympathetic nervous system. <br /> <br /> The medullary region of the adrenal glands is tasked with the endocrine secretions of adrenaline and nor-adrenaline in response to environmental stressors that are signalled for by the sympathetic nervous system. That is, the secretion of fight-or-flight response hormones in order to restrict vasculature to the trunk and increase vascular activity in the peripheral musculature.<br /> <br /> The adrenal glands are supplied by several branches of the great vessels in the abdominal cavity. The secreted catecholamines in the medulla are directly able to pass to the blood stream this way.<br /> <br /> These adrenal glands and their contents are retroperitoneal in the adult and varied in shape, with the left often being semilunar and right being pyramidal. Nervous supply of the adrenal glands is achieved by contributions from the splanchnic nerves of the celiac plexus. <br /> <br /> <br /> [[File:Dd.jpg|500px|thumb|right|Adult Adrenal Glands in situ]] <br /> ----<br /> <br /> ===Molecular mechanisms/factors/genes===<br /> ----<br /> <br /> ====Role of Adrenal Medulla in the Neonate and Adult====<br /> <br /> Understanding the biochemistry of catecholamines is necessary to see how the adrenal medulla is designed in the stages of embryology and how it is suited for life in the neonate and adult. <br /> <br /> The epinephrine and norepinephrine in the neonate and adult work by primarily changing the osmoregulatory state of vasculature in organs. With the exclusion of their neuromodulatory and neurotransmitter functions, epinephrine and norepinephrine are mainly tasked with the control of sympathetic and parasympathetic supplies. <br /> <br /> >Norepinephrine is a constrictor of peripheral vasculature by antagonising the action of surface receptors expressed on the endothelium of blood vessels, specifically Alpha-1 and Alpha-2 receptors, such that vascular resistance increases. <br /> <br /> >Epinephrine is both a vasoconstrictor and vasodilator, depending on what receptors it attaches to. As a non-selective adrenergic agonist, it acts on Alpha-1, Alpha-2, Beta-1, Beta-2 and Beta-3 receptors that are found throughout the body's tissues, yielding many different physiological responses.<br /> <br /> ====Genes and Transcription Factors Involved with the Adrenal Medulla's Development====<br /> <br /> Members of the SOX (SRY-Box) gene family have multiple key contributors to Neural Crest in the Adrenal Medulla.<br /> <br /> Mouse models have demonstrated that SOX-10 knock-outs (mice whose DNA has been engineered to not express SOX-10) do not have an adrenal medulla. There has also been suggestion that SOX-8,9 and 10 are all strongly related to the migratory patterning of neural crest cells to the developing adrenal glands.<br /> <br /> The TH gene (for Tyrosine Hydroxylase) encodes the aforementioned enzyme in the adrenal medulla and central nervous system. Tyrosine Hydroxylase is crucial in biochemical pathways and cascades for the synthesis of catecholamines and other CNS neurotransmitters. The conversion from L-Tyrosine to L-DOPA is dependent upon the catalytic action of Tyrosine Hydroxylase. From there, L-DOPA can make Dopamine and eventually Epinephrine and Norepinephrine as well. <br /> <br /> [[File:Catecholamine_Synthesis.jpg|500px|thumb|right|Cascade of Catecholamine Synthesis]]<br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2291442/<br /> https://www.ncbi.nlm.nih.gov/pubmed/19396395<br /> <br /> ===Abnormalities/abnormal development===<br /> ----<br /> ===Animal models===<br /> ----<br /> Animal models are an integral part of research in embryology. In particular due to the moral concerns regarding the use of humans in scientific research. As a result different animals are used as substitutes to simulate the same environments and hope to achieve results that would also be able to represent humans as well. Prenatal adrenal gland development has been described in a number of scientific reports dating from the 1900s to studies in more recent years. These involved a variety of animal models such as ox, sheep, swine and most commonly mice. <br /> <br /> <br /> There has been extensive research conducted into the adrenal chromaffin cells and their embryological developments. As explained above nueral crest cells are pluripotent meaning they are able to differentiate into multiple different cells. The neural crest cells give rise to chromaffin cells of the adrenal medulla.<br /> Ahonen suggested that some neural crest cells continue migration from the chain ganglia to the lateral sides of aorta, where they form the perirenal ganglia and adrenal medulla, and finally to the ventral side of the aorta to form the preaortic sympathetic tissue. However, that report only showed the several transverse sections of the fetal trunk for the a demonstration of the migration route of neural crest cells. In this study, using three dimensional reconstructed images, we aimed to observe how TH-labeled chromaffin cells penetrate into the adrenal anlage to form the adrenal medulla and whether the migration route of TH - positive cells from the adrenal connects the preaortic sympathetic ganglia <br /> (M.Yamato, R. Yanai, K. Arishima, 2004) <br /> <br /> Prenatal adrenal gland development has been described in numerous published reports covering a wide variety of species, including the ox (Katznelson, 1966; Wrobel and Suss, 1999), sheep (Davies, 1950; Wintour et al., 1975; Upadhyay and Zamboni, 1982; Naaman‐Reperant and Durand, 1997; Grino, 2004), swine (Sokolov et al., 2006) and mouse (Waring, 1935; Ikeda et al., 1994; Sass, 1996; Nyska and Maronpot, 1999; Bland et al., 2003; Val et al., 2007). Adrenal gland development also has been extensively described for humans as well (Kolliker, 1879; Minot, 1892; Zuckerkandl, 1912; Wieman, 1920; Ikeda et al., 1981; Langlois et al., 2002; Hanley and Arit, 2006).<br /> <br /> https://www.sciencedirect.com/science/article/pii/S0925477302004550<br /> http://dev.biologists.org/content/develop/126/13/2935.full.pdf<br /> <br /> ===Current research (labs)===<br /> ----<br /> The findings presented until now have focused on the mechanisms controlling migration along the dorsolateral path. In comparison, our understanding of the mechanisms controlling NCC migration along the ventral path are complicated by the fact that this population comprises multiple precursors that form different derivatives in distinct regions of the embryo. For example, ventrally migrating NCCs either stop within the sclerotome in close association with the neural tube to form neurons and glia of the sensory nervous system (i.e. the dorsal root ganglia [DRG]), while other NCCs continue to migrate further ventrally to form the autonomic nervous system (i.e. sympathetic ganglia and chromaffin cells of the adrenal gland)<br /> <br /> Adrenomedullary chromaffin cells are catecholamine (CA)-producing cells originating from trunk neural crest (NC) via sympathoadrenal progenitors (SAPs). We generated NC and SAPs from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) in vitro via BMP2/FGF2 exposure, ascertained by qPCR and immunoexpression of SOX10, ASCL1, TFAP2α, and PHOX2B, and by fluorescence-activated cell sorting selection for p75NTR and GD2, and confirmed their trunk-like HOX gene expression. We showed that continuing BMP4 and curtailing FGF2 in vitro, augmented with corticosteroid mimetic, induced these cells to upregulate the chromaffin cell-specific marker PNMT and other CA synthesis and storage markers, and we demonstrated noradrenaline and adrenaline by Faglu and high-performance liquid chromatography. We showed these human cells' SAP-like property of migration and differentiation into cells expressing chromaffin cell markers by implanting them into avian embryos in vivo and in chorio-allantoic membrane grafts. These cells have the potential for investigating differentiation of human chromaffin cells and for modeling diseases involving this cell type.<br /> <br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768882/<br /> <br /> ===Glossary===<br /> ----<br /> ===Reference list===</div>

Z5091101 https://embryology.med.unsw.edu.au/embryology/index.php?title=2018_Group_Project_1&diff=355699 2018 Group Project 1 2018-10-07T08:30:34Z

<p>Z5091101: /* History */</p> <hr /> <div>=The Contribution of Neural Crest Cells to the Adrenal Medulla=<br /> ----<br /> {{2018ANAT2341ProjectHeader}}<br /> <br /> <br /> ===Introduction===<br /> [[User:Z5014972|Z5014972]] ([[User talk:Z5014972|talk]]) 12:47, 14 August 2018 (AEST)z5014972 <br /> good review article https://link.springer.com/article/10.1007%2Fs12022-009-9070-6<br /> ----<br /> ===History===<br /> ----<br /> '''Describing the neural crest'''<br /> [[File:Wilhelm_His_History_Wilhelm.jpeg|left|230px|thumb|Wilhelm His]]<br /> The "neural crest" is a structure in the embryo and is the junction between the neural and epidermal ectoderm. The neural crest contributes a large number of cells of varying structure and function that directly or indirectly contribute to the development of tissues and organs within the body {{#pmid:19179766|PMID19179766}}. In 1868, the neural crest cells were first identified in a chick embryo as a collection of cells known as "Zwischenstrang" by Professor Wilhelm His {{#pmid:22820859|PMID22820859}}. Wilhelm His was among the first to provide an explanation for the mechanics governing the developing embryo as well as the physiology and the organs that the differing germinal regions would eventually give rise to. In 1878, the term neural ridge was used to describe this collection of cells but the term neural crest was later coined by Arthur Milnes Marshall in 1879 in a paper he worked on disseminating the knowledge from his research on the development of cranial nerves in chicken embryos. {{#pmid:19179766|PMID19179766}}.<br /> [[File:NC Location.jpg|left|500px|thumb|The neural crest]]<br /> <br /> '''1890s-1950s'''<br /> The neural crest is the point of origin for spinal/cranial ganglia and neurons. This theory received little criticism and was not contested much by other researchers prior to the 1890s. This is owing to the fact that the neural crest is quite closely related to the neural tube and thus this relationship makes sense. This discovery was made by His and Marshall, however, they found this out independently of one another.In the 1890s, Julia Platt, claimed that odontoblasts as well as the cartilages forming the facial and pharyngeal arch skeletons came from the ectoderm. This created much debate and was contested by many. <br /> <br /> This is because this theory completely contradicted the germ-layer theory, whereby skeletal tissues originate at the mesoderm and not the ectoderm. The controversies this finding created brought about a slowing down of research, as demonstrated by a gap of almost 40 years between the theory that skeletal tissues originating from the neural crest. Today, it is known that the neural crest does indeed play a role in the development of the skeleton in vertebrates, particularly, the cranial neural crest. Although these studies were occurring, the focus was still primarily on researching pigment cells and ganglia of the spine up until the 1950s, when Sven Hörstadius' major work on the neural crest was published, titled "The Neural Crest: Its properties and derivatives in the light of experimental research". This work focused on experimental data tracing the development of the cartilaginous skeleton derived from the neural crest {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1960s - 1970s'''<br /> In the 1960s, the migration patterns of neural crest cells were studied in avian embryos (birds). This was a shift from studying the embryos of amphibians. This was inspired by studies conducted in the 1960s on neural crest cells migrating from the brain and spinal cord, known as trunk and cranial neural crest cells {{#pmid:19179766|PMID19179766}}. The cranial neural crest eventually becomes the bones, cartilage and connective tissues forming the foundation of the face, ears and teeth. The trunk neural crest cells can either become melanocytes or can migrate into sclerotomes which are later contributors to the cartilage of the spine and the dorsal root ganglia {{#pmid:22820859|PMID22820859}}. The cells in the trunk neural crest that migrate vertically become the sympathetic ganglia, the nerves proximal to the aorta and the adrenal medulla <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. In the 1970s many detailed maps signifying the pathways of many of the neural crest cells appeared as well as an understanding that the environment in which the neural crest cells are found plays a major role in their final development as well as the occurrences of abnormalities in the fetus {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1980s - 21st century'''<br /> From the 1980s-1990s, the causative agent of organ transformation from one to another (homeotic patterning), as well as the Hox genes which regulate the axis of most symmetrical animal embryos were founded and studied. The neural crest, which previously was divided into the cranial and trunk regions, was now further divided into the vagal and sacral neural crest, the cardiac neural crest and the cephalic neural crest {{#pmid:19179766|PMID19179766}}. The vagal & sacral neural crest gives rise to the parasympathetic ganglia found in the gut. Without these ganglia, peristalsis, is not possible <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. The cardiac neural crest contributes to the valves, septa and major blood vessels of the heart, as well as connective tissues and cartilage{{#pmid:19179766|PMID19179766}}. This is important for the structure of the heart as well as its overall function, enabling it to move blood around the body efficiently as well as keep pulmonary and aortic circulation separated <ref name=Gilbert2000>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Neural Crest. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10065/</ref>. <br /> <br /> [[File:Regions_of_NC_Cells.jpg|left|Neural crest regions|thumb]]<br /> Today, knowledge of the neural crest cells, their migration patterns, modes of differentiation, derivatives and apoptosis (cell death) are being studied extensively. This is being done on a comparative basis between different organisms, to add further evidence for evolution {{#pmid:19179766|PMID19179766}}. The neural crest is definitely forging a "crest" between the fields of developmental and evolutionary biology, as it is a structure '''shared exclusively by all vertebrates'''. Invertebrates do not derive their specialised cells from the neural crest as they do not have one, rather, they derive these from the endomesoderm {{#pmid:22230617|PMID22230617}}.<br /> <br /> ===Embryonic origins===<br /> ----<br /> https://www.ncbi.nlm.nih.gov/books/NBK10065/<br /> <br /> ===Developmental time course===<br /> ----<br /> <br /> The adrenal gland has two distinct sections, the cortex and the medulla, both with different embryonic origins. The cortex accounts for 90% of the adrenal glands and arises from intermediate mesoderm. The medulla only accounts for 10% of the adult adrenal glands, however it has neural crest embryonic origin. The medulla consists of chromaffinoblast cells which are migrant neuroblast cells from the neural crest, therefore the adrenal medulla is a component of the sympathetic nervous system.{{#pmid:21175739|PMID21175739}} Neural crest cells replicate in week 7 and begin to differentiate in week 8, the cells then migrate to the developing adrenal gland in week 9 of development.{{#pmid:25255746|PMID25255746}}{{#pmid:18279781|PMID18279781}} The neural crest cells infiltrate the cortex and the chromaffin cells are scattered islands in the cortex.{{#pmid:23354096|PMID23354096}} Throughout development the cells will become more compact in the centre of the gland, during this period of development the adrenal gland is growing rapidly. The gland is abnormally large until the second trimester and the medulla is much thicker prenatally.{{#pmid:18279781|PMID18279781}}{{#pmid:21175739|PMID21175739}}<br /> <br /> ===Developmental/adult function===<br /> ----<br /> ===Tissue/organ structure===<br /> <br /> ====Normal Structure and Function of the Adrenal Medulla====<br /> <br /> The cells of the adrenal medulla are derived from the neural crest as opposed to the mesodermal origins of the cortex. The medulla contains secretory cells called chromaffin cells, due to the agents they produce when oxidised, such as chromate. These cells secrete epinephrine and norepinephrine in response to various substances such as acetylcholine.<br /> <br /> There are three types of cells in the adult adrenal medulla: <br /> 1) Epinephrine cells<br /> 2) Norepinephrine cells <br /> 3) Small granule-containing cells (SGCs)<br /> These cells also produce various other peptides such as substance P and neurotensin. The adrenal medulla also contains presynaptic sympathetic ganglion cells. <br /> <br /> <br /> ====Related Anatomy====<br /> <br /> The tissue and organ structure of the adrenal medulla should be understood with regard to its specialised function within the sympathetic nervous system. <br /> <br /> The medullary region of the adrenal glands is tasked with the endocrine secretions of adrenaline and nor-adrenaline in response to environmental stressors that are signalled for by the sympathetic nervous system. That is, the secretion of fight-or-flight response hormones in order to restrict vasculature to the trunk and increase vascular activity in the peripheral musculature.<br /> <br /> The adrenal glands are supplied by several branches of the great vessels in the abdominal cavity. The secreted catecholamines in the medulla are directly able to pass to the blood stream this way.<br /> <br /> These adrenal glands and their contents are retroperitoneal in the adult and varied in shape, with the left often being semilunar and right being pyramidal. Nervous supply of the adrenal glands is achieved by contributions from the splanchnic nerves of the celiac plexus. <br /> <br /> <br /> [[File:Dd.jpg|500px|thumb|right|Adult Adrenal Glands in situ]] <br /> ----<br /> <br /> ===Molecular mechanisms/factors/genes===<br /> ----<br /> <br /> ====Role of Adrenal Medulla in the Neonate and Adult====<br /> <br /> Understanding the biochemistry of catecholamines is necessary to see how the adrenal medulla is designed in the stages of embryology and how it is suited for life in the neonate and adult. <br /> <br /> The epinephrine and norepinephrine in the neonate and adult work by primarily changing the osmoregulatory state of vasculature in organs. With the exclusion of their neuromodulatory and neurotransmitter functions, epinephrine and norepinephrine are mainly tasked with the control of sympathetic and parasympathetic supplies. <br /> <br /> >Norepinephrine is a constrictor of peripheral vasculature by antagonising the action of surface receptors expressed on the endothelium of blood vessels, specifically Alpha-1 and Alpha-2 receptors, such that vascular resistance increases. <br /> <br /> >Epinephrine is both a vasoconstrictor and vasodilator, depending on what receptors it attaches to. As a non-selective adrenergic agonist, it acts on Alpha-1, Alpha-2, Beta-1, Beta-2 and Beta-3 receptors that are found throughout the body's tissues, yielding many different physiological responses.<br /> <br /> ====Genes and Transcription Factors Involved with the Adrenal Medulla's Development====<br /> <br /> Members of the SOX (SRY-Box) gene family have multiple key contributors to Neural Crest in the Adrenal Medulla.<br /> <br /> Mouse models have demonstrated that SOX-10 knock-outs (mice whose DNA has been engineered to not express SOX-10) do not have an adrenal medulla. There has also been suggestion that SOX-8,9 and 10 are all strongly related to the migratory patterning of neural crest cells to the developing adrenal glands.<br /> <br /> The TH gene (for Tyrosine Hydroxylase) encodes the aforementioned enzyme in the adrenal medulla and central nervous system. Tyrosine Hydroxylase is crucial in biochemical pathways and cascades for the synthesis of catecholamines and other CNS neurotransmitters. The conversion from L-Tyrosine to L-DOPA is dependent upon the catalytic action of Tyrosine Hydroxylase. From there, L-DOPA can make Dopamine and eventually Epinephrine and Norepinephrine as well. <br /> <br /> [[File:Catecholamine_Synthesis.jpg|500px|thumb|right|Cascade of Catecholamine Synthesis]]<br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2291442/<br /> https://www.ncbi.nlm.nih.gov/pubmed/19396395<br /> <br /> ===Abnormalities/abnormal development===<br /> ----<br /> ===Animal models===<br /> ----<br /> Animal models are an integral part of research in embryology. In particular due to the moral concerns regarding the use of humans in scientific research. As a result different animals are used as substitutes to simulate the same environments and hope to achieve results that would also be able to represent humans as well. Prenatal adrenal gland development has been described in a number of scientific reports dating from the 1900s to studies in more recent years. These involved a variety of animal models such as ox, sheep, swine and most commonly mice. <br /> <br /> <br /> There has been extensive research conducted into the adrenal chromaffin cells and their embryological developments. As explained above nueral crest cells are pluripotent meaning they are able to differentiate into multiple different cells. The neural crest cells give rise to chromaffin cells of the adrenal medulla.<br /> Ahonen suggested that some neural crest cells continue migration from the chain ganglia to the lateral sides of aorta, where they form the perirenal ganglia and adrenal medulla, and finally to the ventral side of the aorta to form the preaortic sympathetic tissue. However, that report only showed the several transverse sections of the fetal trunk for the a demonstration of the migration route of neural crest cells. In this study, using three dimensional reconstructed images, we aimed to observe how TH-labeled chromaffin cells penetrate into the adrenal anlage to form the adrenal medulla and whether the migration route of TH - positive cells from the adrenal connects the preaortic sympathetic ganglia <br /> (M.Yamato, R. Yanai, K. Arishima, 2004) <br /> <br /> Prenatal adrenal gland development has been described in numerous published reports covering a wide variety of species, including the ox (Katznelson, 1966; Wrobel and Suss, 1999), sheep (Davies, 1950; Wintour et al., 1975; Upadhyay and Zamboni, 1982; Naaman‐Reperant and Durand, 1997; Grino, 2004), swine (Sokolov et al., 2006) and mouse (Waring, 1935; Ikeda et al., 1994; Sass, 1996; Nyska and Maronpot, 1999; Bland et al., 2003; Val et al., 2007). Adrenal gland development also has been extensively described for humans as well (Kolliker, 1879; Minot, 1892; Zuckerkandl, 1912; Wieman, 1920; Ikeda et al., 1981; Langlois et al., 2002; Hanley and Arit, 2006).<br /> <br /> https://www.sciencedirect.com/science/article/pii/S0925477302004550<br /> http://dev.biologists.org/content/develop/126/13/2935.full.pdf<br /> <br /> ===Current research (labs)===<br /> ----<br /> The findings presented until now have focused on the mechanisms controlling migration along the dorsolateral path. In comparison, our understanding of the mechanisms controlling NCC migration along the ventral path are complicated by the fact that this population comprises multiple precursors that form different derivatives in distinct regions of the embryo. For example, ventrally migrating NCCs either stop within the sclerotome in close association with the neural tube to form neurons and glia of the sensory nervous system (i.e. the dorsal root ganglia [DRG]), while other NCCs continue to migrate further ventrally to form the autonomic nervous system (i.e. sympathetic ganglia and chromaffin cells of the adrenal gland)<br /> <br /> Adrenomedullary chromaffin cells are catecholamine (CA)-producing cells originating from trunk neural crest (NC) via sympathoadrenal progenitors (SAPs). We generated NC and SAPs from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) in vitro via BMP2/FGF2 exposure, ascertained by qPCR and immunoexpression of SOX10, ASCL1, TFAP2α, and PHOX2B, and by fluorescence-activated cell sorting selection for p75NTR and GD2, and confirmed their trunk-like HOX gene expression. We showed that continuing BMP4 and curtailing FGF2 in vitro, augmented with corticosteroid mimetic, induced these cells to upregulate the chromaffin cell-specific marker PNMT and other CA synthesis and storage markers, and we demonstrated noradrenaline and adrenaline by Faglu and high-performance liquid chromatography. We showed these human cells' SAP-like property of migration and differentiation into cells expressing chromaffin cell markers by implanting them into avian embryos in vivo and in chorio-allantoic membrane grafts. These cells have the potential for investigating differentiation of human chromaffin cells and for modeling diseases involving this cell type.<br /> <br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768882/<br /> <br /> ===Glossary===<br /> ----<br /> ===Reference list===</div>

Z5091101 https://embryology.med.unsw.edu.au/embryology/index.php?title=2018_Group_Project_1&diff=355697 2018 Group Project 1 2018-10-07T07:30:01Z

<p>Z5091101: /* History */</p> <hr /> <div>=The Contribution of Neural Crest Cells to the Adrenal Medulla=<br /> ----<br /> {{2018ANAT2341ProjectHeader}}<br /> <br /> <br /> ===Introduction===<br /> [[User:Z5014972|Z5014972]] ([[User talk:Z5014972|talk]]) 12:47, 14 August 2018 (AEST)z5014972 <br /> good review article https://link.springer.com/article/10.1007%2Fs12022-009-9070-6<br /> ----<br /> ===History===<br /> ----<br /> '''Describing the neural crest'''<br /> [[File:Wilhelm_His_History_Wilhelm.jpeg|left|230px|thumb|Wilhelm His]]<br /> The "neural crest" is a structure in the embryo and is the junction between the neural and epidermal ectoderm. The neural crest contributes a large number of cells of varying structure and function that directly or indirectly contribute to the development of tissues and organs within the body {{#pmid:19179766|PMID19179766}}. In 1868, the neural crest cells were first identified in a chick embryo as a collection of cells known as "Zwischenstrang" by Professor Wilhelm His {{#pmid:22820859|PMID22820859}}. Wilhelm His was among the first to provide an explanation for the mechanics governing the developing embryo as well as the physiology and the organs that the differing germinal regions would eventually give rise to. In 1878, the term neural ridge was used to describe this collection of cells but the term neural crest was later coined by Arthur Milnes Marshall in 1879 in a paper he worked on disseminating the knowledge from his research on the development of cranial nerves in chicken embryos. {{#pmid:19179766|PMID19179766}}.<br /> [[File:NC Location.jpg|left|500px|thumb|The neural crest]]<br /> <br /> '''1890s-1950s'''<br /> The neural crest is the point of origin for spinal/cranial ganglia and neurons. This theory received little criticism and was not contested much by other researchers prior to the 1890s. This is owing to the fact that the neural crest is quite closely related to the neural tube and thus this relationship makes sense. This discovery was made by His and Marshall, however, they found this out independently of one another.In the 1890s, Julia Platt, claimed that odontoblasts as well as the cartilages forming the facial and pharyngeal arch skeletons came from the ectoderm. This created much debate and was contested by many. <br /> <br /> This is because this theory completely contradicted the germ-layer theory, whereby skeletal tissues originate at the mesoderm and not the ectoderm. The controversies this finding created brought about a slowing down of research, as demonstrated by a gap of almost 40 years between the theory that skeletal tissues originating from the neural crest. Today, it is known that the neural crest does indeed play a role in the development of the skeleton in vertebrates, particularly, the cranial neural crest. Although these studies were occurring, the focus was still primarily on researching pigment cells and ganglia of the spine up until the 1950s, when Sven Hörstadius' major work on the neural crest was published, titled "The Neural Crest: Its properties and derivatives in the light of experimental research". This work focused on experimental data tracing the development of the cartilaginous skeleton derived from the neural crest {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1960s - 1970s'''<br /> In the 1960s, the migration patterns of neural crest cells were studied in avian embryos (birds). This was a shift from studying the embryos of amphibians. This was inspired by studies conducted in the 1960s on neural crest cells migrating from the brain and spinal cord, known as trunk and cranial neural crest cells {{#pmid:19179766|PMID19179766}}. The cranial neural crest eventually becomes the bones, cartilage and connective tissues forming the foundation of the face, ears and teeth. The trunk neural crest cells can either become melanocytes or can migrate into sclerotomes which are later contributors to the cartilage of the spine and the dorsal root ganglia {{#pmid:22820859|PMID22820859}}. The cells in the trunk neural crest that migrate vertically become the sympathetic ganglia, the nerves proximal to the aorta and the adrenal medulla '''[W]'''. In the 1970s many detailed maps signifying the pathways of many of the neural crest cells appeared as well as an understanding that the environment in which the neural crest cells are found plays a major role in their final development as well as the occurrences of abnormalities in the fetus {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1980s - 21st century'''<br /> From the 1980s-1990s, the causative agent of organ transformation from one to another (homeotic patterning), as well as the Hox genes which regulate the axis of most symmetrical animal embryos were founded and studied. The neural crest, which previously was divided into the cranial and trunk regions, was now further divided into the vagal and sacral neural crest, the cardiac neural crest and the cephalic neural crest {{#pmid:19179766|PMID19179766}}. The vagal & sacral neural crest gives rise to the parasympathetic ganglia found in the gut. Without these ganglia, peristalsis, is not possible '''[W]'''. The cardiac neural crest contributes to the valves, septa and major blood vessels of the heart, as well as connective tissues and cartilage{{#pmid:19179766|PMID19179766}}. This is important for the structure of the heart as well as its overall function, enabling it to move blood around the body efficiently as well as keep pulmonary and aortic circulation separated '''[W]'''. <br /> <br /> [[File:Regions_of_NC_Cells.jpg|left|Neural crest regions|thumb]]<br /> Today, knowledge of the neural crest cells, their migration patterns, modes of differentiation, derivatives and apoptosis (cell death) are being studied extensively. This is being done on a comparative basis between different organisms, to add further evidence for evolution {{#pmid:19179766|PMID19179766}}. The neural crest is definitely forging a "crest" between the fields of developmental and evolutionary biology, as it is a structure '''shared exclusively by all vertebrates'''. Invertebrates do not derive their specialised cells from the neural crest as they do not have one, rather, they derive these from the endomesoderm {{#pmid:22230617|PMID22230617}}.<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> '''[W]''' - need to reference: https://www.ncbi.nlm.nih.gov/books/NBK10065/<br /> <br /> ===Embryonic origins===<br /> ----<br /> https://www.ncbi.nlm.nih.gov/books/NBK10065/<br /> <br /> ===Developmental time course===<br /> ----<br /> <br /> The adrenal gland has two distinct sections, the cortex and the medulla, both with different embryonic origins. The cortex accounts for 90% of the adrenal glands and arises from intermediate mesoderm. The medulla only accounts for 10% of the adult adrenal glands, however it has neural crest embryonic origin. The medulla consists of chromaffinoblast cells which are migrant neuroblast cells from the neural crest, therefore the adrenal medulla is a component of the sympathetic nervous system.{{#pmid:21175739|PMID21175739}} Neural crest cells replicate in week 7 and begin to differentiate in week 8, the cells then migrate to the developing adrenal gland in week 9 of development.{{#pmid:25255746|PMID25255746}}{{#pmid:18279781|PMID18279781}} The neural crest cells infiltrate the cortex and the chromaffin cells are scattered islands in the cortex.{{#pmid:23354096|PMID23354096}} Throughout development the cells will become more compact in the centre of the gland, during this period of development the adrenal gland is growing rapidly. The gland is abnormally large until the second trimester and the medulla is much thicker prenatally.{{#pmid:18279781|PMID18279781}}{{#pmid:21175739|PMID21175739}}<br /> <br /> ===Developmental/adult function===<br /> ----<br /> ===Tissue/organ structure===<br /> <br /> ====Normal Structure and Function of the Adrenal Medulla====<br /> <br /> The cells of the adrenal medulla are derived from the neural crest as opposed to the mesodermal origins of the cortex. The medulla contains secretory cells called chromaffin cells, due to the agents they produce when oxidised, such as chromate. These cells secrete epinephrine and norepinephrine in response to various substances such as acetylcholine.<br /> <br /> There are three types of cells in the adult adrenal medulla: <br /> 1) Epinephrine cells<br /> 2) Norepinephrine cells <br /> 3) Small granule-containing cells (SGCs)<br /> These cells also produce various other peptides such as substance P and neurotensin. The adrenal medulla also contains presynaptic sympathetic ganglion cells. <br /> <br /> <br /> ====Related Anatomy====<br /> <br /> The tissue and organ structure of the adrenal medulla should be understood with regard to its specialised function within the sympathetic nervous system. <br /> <br /> The medullary region of the adrenal glands is tasked with the endocrine secretions of adrenaline and nor-adrenaline in response to environmental stressors that are signalled for by the sympathetic nervous system. That is, the secretion of fight-or-flight response hormones in order to restrict vasculature to the trunk and increase vascular activity in the peripheral musculature.<br /> <br /> The adrenal glands are supplied by several branches of the great vessels in the abdominal cavity. The secreted catecholamines in the medulla are directly able to pass to the blood stream this way.<br /> <br /> These adrenal glands and their contents are retroperitoneal in the adult and varied in shape, with the left often being semilunar and right being pyramidal. Nervous supply of the adrenal glands is achieved by contributions from the splanchnic nerves of the celiac plexus. <br /> <br /> <br /> [[File:Dd.jpg|500px|thumb|right|Adult Adrenal Glands in situ]] <br /> ----<br /> <br /> ===Molecular mechanisms/factors/genes===<br /> ----<br /> <br /> ====Role of Adrenal Medulla in the Neonate and Adult====<br /> <br /> Understanding the biochemistry of catecholamines is necessary to see how the adrenal medulla is designed in the stages of embryology and how it is suited for life in the neonate and adult. <br /> <br /> The epinephrine and norepinephrine in the neonate and adult work by primarily changing the osmoregulatory state of vasculature in organs. With the exclusion of their neuromodulatory and neurotransmitter functions, epinephrine and norepinephrine are mainly tasked with the control of sympathetic and parasympathetic supplies. <br /> <br /> >Norepinephrine is a constrictor of peripheral vasculature by antagonising the action of surface receptors expressed on the endothelium of blood vessels, specifically Alpha-1 and Alpha-2 receptors, such that vascular resistance increases. <br /> <br /> >Epinephrine is both a vasoconstrictor and vasodilator, depending on what receptors it attaches to. As a non-selective adrenergic agonist, it acts on Alpha-1, Alpha-2, Beta-1, Beta-2 and Beta-3 receptors that are found throughout the body's tissues, yielding many different physiological responses.<br /> <br /> ====Genes and Transcription Factors Involved with the Adrenal Medulla's Development====<br /> <br /> Members of the SOX (SRY-Box) gene family have multiple key contributors to Neural Crest in the Adrenal Medulla.<br /> <br /> Mouse models have demonstrated that SOX-10 knock-outs (mice whose DNA has been engineered to not express SOX-10) do not have an adrenal medulla. There has also been suggestion that SOX-8,9 and 10 are all strongly related to the migratory patterning of neural crest cells to the developing adrenal glands.<br /> <br /> The TH gene (for Tyrosine Hydroxylase) encodes the aforementioned enzyme in the adrenal medulla and central nervous system. Tyrosine Hydroxylase is crucial in biochemical pathways and cascades for the synthesis of catecholamines and other CNS neurotransmitters. The conversion from L-Tyrosine to L-DOPA is dependent upon the catalytic action of Tyrosine Hydroxylase. From there, L-DOPA can make Dopamine and eventually Epinephrine and Norepinephrine as well. <br /> <br /> [[File:Catecholamine_Synthesis.jpg|500px|thumb|right|Cascade of Catecholamine Synthesis]]<br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2291442/<br /> https://www.ncbi.nlm.nih.gov/pubmed/19396395<br /> <br /> ===Abnormalities/abnormal development===<br /> ----<br /> ===Animal models===<br /> ----<br /> Animal models are an integral part of research in embryology. In particular due to the moral concerns regarding the use of humans in scientific research. As a result different animals are used as substitutes to simulate the same environments and hope to achieve results that would also be able to represent humans as well. Prenatal adrenal gland development has been described in a number of scientific reports dating from the 1900s to studies in more recent years. These involved a variety of animal models such as ox, sheep, swine and most commonly mice. <br /> <br /> <br /> There has been extensive research conducted into the adrenal chromaffin cells and their embryological developments. As explained above nueral crest cells are pluripotent meaning they are able to differentiate into multiple different cells. The neural crest cells give rise to chromaffin cells of the adrenal medulla.<br /> Ahonen suggested that some neural crest cells continue migration from the chain ganglia to the lateral sides of aorta, where they form the perirenal ganglia and adrenal medulla, and finally to the ventral side of the aorta to form the preaortic sympathetic tissue. However, that report only showed the several transverse sections of the fetal trunk for the a demonstration of the migration route of neural crest cells. In this study, using three dimensional reconstructed images, we aimed to observe how TH-labeled chromaffin cells penetrate into the adrenal anlage to form the adrenal medulla and whether the migration route of TH - positive cells from the adrenal connects the preaortic sympathetic ganglia <br /> (M.Yamato, R. Yanai, K. Arishima, 2004) <br /> <br /> Prenatal adrenal gland development has been described in numerous published reports covering a wide variety of species, including the ox (Katznelson, 1966; Wrobel and Suss, 1999), sheep (Davies, 1950; Wintour et al., 1975; Upadhyay and Zamboni, 1982; Naaman‐Reperant and Durand, 1997; Grino, 2004), swine (Sokolov et al., 2006) and mouse (Waring, 1935; Ikeda et al., 1994; Sass, 1996; Nyska and Maronpot, 1999; Bland et al., 2003; Val et al., 2007). Adrenal gland development also has been extensively described for humans as well (Kolliker, 1879; Minot, 1892; Zuckerkandl, 1912; Wieman, 1920; Ikeda et al., 1981; Langlois et al., 2002; Hanley and Arit, 2006).<br /> <br /> https://www.sciencedirect.com/science/article/pii/S0925477302004550<br /> http://dev.biologists.org/content/develop/126/13/2935.full.pdf<br /> <br /> ===Current research (labs)===<br /> ----<br /> The findings presented until now have focused on the mechanisms controlling migration along the dorsolateral path. In comparison, our understanding of the mechanisms controlling NCC migration along the ventral path are complicated by the fact that this population comprises multiple precursors that form different derivatives in distinct regions of the embryo. For example, ventrally migrating NCCs either stop within the sclerotome in close association with the neural tube to form neurons and glia of the sensory nervous system (i.e. the dorsal root ganglia [DRG]), while other NCCs continue to migrate further ventrally to form the autonomic nervous system (i.e. sympathetic ganglia and chromaffin cells of the adrenal gland)<br /> <br /> Adrenomedullary chromaffin cells are catecholamine (CA)-producing cells originating from trunk neural crest (NC) via sympathoadrenal progenitors (SAPs). We generated NC and SAPs from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) in vitro via BMP2/FGF2 exposure, ascertained by qPCR and immunoexpression of SOX10, ASCL1, TFAP2α, and PHOX2B, and by fluorescence-activated cell sorting selection for p75NTR and GD2, and confirmed their trunk-like HOX gene expression. We showed that continuing BMP4 and curtailing FGF2 in vitro, augmented with corticosteroid mimetic, induced these cells to upregulate the chromaffin cell-specific marker PNMT and other CA synthesis and storage markers, and we demonstrated noradrenaline and adrenaline by Faglu and high-performance liquid chromatography. We showed these human cells' SAP-like property of migration and differentiation into cells expressing chromaffin cell markers by implanting them into avian embryos in vivo and in chorio-allantoic membrane grafts. These cells have the potential for investigating differentiation of human chromaffin cells and for modeling diseases involving this cell type.<br /> <br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768882/<br /> <br /> ===Glossary===<br /> ----<br /> ===Reference list===</div>

Z5091101 https://embryology.med.unsw.edu.au/embryology/index.php?title=2018_Group_Project_1&diff=355695 2018 Group Project 1 2018-10-07T07:29:25Z

<p>Z5091101: /* History */</p> <hr /> <div>=The Contribution of Neural Crest Cells to the Adrenal Medulla=<br /> ----<br /> {{2018ANAT2341ProjectHeader}}<br /> <br /> <br /> ===Introduction===<br /> [[User:Z5014972|Z5014972]] ([[User talk:Z5014972|talk]]) 12:47, 14 August 2018 (AEST)z5014972 <br /> good review article https://link.springer.com/article/10.1007%2Fs12022-009-9070-6<br /> ----<br /> ===History===<br /> ----<br /> '''Describing the neural crest'''<br /> [[File:Wilhelm_His_History_Wilhelm.jpeg|left|230px|thumb|Wilhelm His]]<br /> The "neural crest" is a structure in the embryo and is the junction between the neural and epidermal ectoderm. The neural crest contributes a large number of cells of varying structure and function that directly or indirectly contribute to the development of tissues and organs within the body {{#pmid:19179766|PMID19179766}}. In 1868, the neural crest cells were first identified in a chick embryo as a collection of cells known as "Zwischenstrang" by Professor Wilhelm His {{#pmid:22820859|PMID22820859}}. Wilhelm His was among the first to provide an explanation for the mechanics governing the developing embryo as well as the physiology and the organs that the differing germinal regions would eventually give rise to. In 1878, the term neural ridge was used to describe this collection of cells but the term neural crest was later coined by Arthur Milnes Marshall in 1879 in a paper he worked on disseminating the knowledge from his research on the development of cranial nerves in chicken embryos. {{#pmid:19179766|PMID19179766}}.<br /> [[File:NC Location.jpg|left|500px|thumb|The neural crest]]<br /> <br /> '''1890s-1950s'''<br /> The neural crest is the point of origin for spinal/cranial ganglia and neurons. This theory received little criticism and was not contested much by other researchers prior to the 1890s. This is owing to the fact that the neural crest is quite closely related to the neural tube and thus this relationship makes sense. This discovery was made by His and Marshall, however, they found this out independently of one another.In the 1890s, Julia Platt, claimed that odontoblasts as well as the cartilages forming the facial and pharyngeal arch skeletons came from the ectoderm. This created much debate and was contested by many. <br /> <br /> This is because this theory completely contradicted the germ-layer theory, whereby skeletal tissues originate at the mesoderm and not the ectoderm. The controversies this finding created brought about a slowing down of research, as demonstrated by a gap of almost 40 years between the theory that skeletal tissues originating from the neural crest. Today, it is known that the neural crest does indeed play a role in the development of the skeleton in vertebrates, particularly, the cranial neural crest. Although these studies were occurring, the focus was still primarily on researching pigment cells and ganglia of the spine up until the 1950s, when Sven Hörstadius' major work on the neural crest was published, titled "The Neural Crest: Its properties and derivatives in the light of experimental research". This work focused on experimental data tracing the development of the cartilaginous skeleton derived from the neural crest {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1960s - 1970s'''<br /> In the 1960s, the migration patterns of neural crest cells were studied in avian embryos (birds). This was a shift from studying the embryos of amphibians. This was inspired by studies conducted in the 1960s on neural crest cells migrating from the brain and spinal cord, known as trunk and cranial neural crest cells {{#pmid:19179766|PMID19179766}}. The cranial neural crest eventually becomes the bones, cartilage and connective tissues forming the foundation of the face, ears and teeth. The trunk neural crest cells can either become melanocytes or can migrate into sclerotomes which are later contributors to the cartilage of the spine and the dorsal root ganglia {{#pmid:22820859|PMID22820859}}. The cells in the trunk neural crest that migrate vertically become the sympathetic ganglia, the nerves proximal to the aorta and the adrenal medulla '''[W]'''. In the 1970s many detailed maps signifying the pathways of many of the neural crest cells appeared as well as an understanding that the environment in which the neural crest cells are found plays a major role in their final development as well as the occurrences of abnormalities in the fetus {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1980s - 21st century'''<br /> From the 1980s-1990s, the causative agent of organ transformation from one to another (homeotic patterning), as well as the Hox genes which regulate the axis of most symmetrical animal embryos were founded and studied. The neural crest, which previously was divided into the cranial and trunk regions, was now further divided into the vagal and sacral neural crest, the cardiac neural crest and the cephalic neural crest {{#pmid:19179766|PMID19179766}}. The vagal & sacral neural crest gives rise to the parasympathetic ganglia found in the gut. Without these ganglia, peristalsis, is not possible '''[W]'''. The cardiac neural crest contributes to the valves, septa and major blood vessels of the heart, as well as connective tissues and cartilage{{#pmid:19179766|PMID19179766}}. This is important for the structure of the heart as well as its overall function, enabling it to move blood around the body efficiently as well as keep pulmonary and aortic circulation separated '''[W]'''. <br /> <br /> Today, knowledge of the neural crest cells, their migration patterns, modes of differentiation, derivatives and apoptosis (cell death) are being studied extensively. This is being done on a comparative basis between different organisms, to add further evidence for evolution {{#pmid:19179766|PMID19179766}}. The neural crest is definitely forging a "crest" between the fields of developmental and evolutionary biology, as it is a structure '''shared exclusively by all vertebrates'''. Invertebrates do not derive their specialised cells from the neural crest as they do not have one, rather, they derive these from the endomesoderm {{#pmid:22230617|PMID22230617}}.<br /> <br /> [[File:Regions_of_NC_Cells.jpg|left|250px|Neural crest regions]]<br /> <br /> <br /> <br /> <br /> <br /> <br /> '''[W]''' - need to reference: https://www.ncbi.nlm.nih.gov/books/NBK10065/<br /> <br /> ===Embryonic origins===<br /> ----<br /> https://www.ncbi.nlm.nih.gov/books/NBK10065/<br /> <br /> ===Developmental time course===<br /> ----<br /> <br /> The adrenal gland has two distinct sections, the cortex and the medulla, both with different embryonic origins. The cortex accounts for 90% of the adrenal glands and arises from intermediate mesoderm. The medulla only accounts for 10% of the adult adrenal glands, however it has neural crest embryonic origin. The medulla consists of chromaffinoblast cells which are migrant neuroblast cells from the neural crest, therefore the adrenal medulla is a component of the sympathetic nervous system.{{#pmid:21175739|PMID21175739}} Neural crest cells replicate in week 7 and begin to differentiate in week 8, the cells then migrate to the developing adrenal gland in week 9 of development.{{#pmid:25255746|PMID25255746}}{{#pmid:18279781|PMID18279781}} The neural crest cells infiltrate the cortex and the chromaffin cells are scattered islands in the cortex.{{#pmid:23354096|PMID23354096}} Throughout development the cells will become more compact in the centre of the gland, during this period of development the adrenal gland is growing rapidly. The gland is abnormally large until the second trimester and the medulla is much thicker prenatally.{{#pmid:18279781|PMID18279781}}{{#pmid:21175739|PMID21175739}}<br /> <br /> ===Developmental/adult function===<br /> ----<br /> ===Tissue/organ structure===<br /> <br /> ====Normal Structure and Function of the Adrenal Medulla====<br /> <br /> The cells of the adrenal medulla are derived from the neural crest as opposed to the mesodermal origins of the cortex. The medulla contains secretory cells called chromaffin cells, due to the agents they produce when oxidised, such as chromate. These cells secrete epinephrine and norepinephrine in response to various substances such as acetylcholine.<br /> <br /> There are three types of cells in the adult adrenal medulla: <br /> 1) Epinephrine cells<br /> 2) Norepinephrine cells <br /> 3) Small granule-containing cells (SGCs)<br /> These cells also produce various other peptides such as substance P and neurotensin. The adrenal medulla also contains presynaptic sympathetic ganglion cells. <br /> <br /> <br /> ====Related Anatomy====<br /> <br /> The tissue and organ structure of the adrenal medulla should be understood with regard to its specialised function within the sympathetic nervous system. <br /> <br /> The medullary region of the adrenal glands is tasked with the endocrine secretions of adrenaline and nor-adrenaline in response to environmental stressors that are signalled for by the sympathetic nervous system. That is, the secretion of fight-or-flight response hormones in order to restrict vasculature to the trunk and increase vascular activity in the peripheral musculature.<br /> <br /> The adrenal glands are supplied by several branches of the great vessels in the abdominal cavity. The secreted catecholamines in the medulla are directly able to pass to the blood stream this way.<br /> <br /> These adrenal glands and their contents are retroperitoneal in the adult and varied in shape, with the left often being semilunar and right being pyramidal. Nervous supply of the adrenal glands is achieved by contributions from the splanchnic nerves of the celiac plexus. <br /> <br /> <br /> [[File:Dd.jpg|500px|thumb|right|Adult Adrenal Glands in situ]] <br /> ----<br /> <br /> ===Molecular mechanisms/factors/genes===<br /> ----<br /> <br /> ====Role of Adrenal Medulla in the Neonate and Adult====<br /> <br /> Understanding the biochemistry of catecholamines is necessary to see how the adrenal medulla is designed in the stages of embryology and how it is suited for life in the neonate and adult. <br /> <br /> The epinephrine and norepinephrine in the neonate and adult work by primarily changing the osmoregulatory state of vasculature in organs. With the exclusion of their neuromodulatory and neurotransmitter functions, epinephrine and norepinephrine are mainly tasked with the control of sympathetic and parasympathetic supplies. <br /> <br /> >Norepinephrine is a constrictor of peripheral vasculature by antagonising the action of surface receptors expressed on the endothelium of blood vessels, specifically Alpha-1 and Alpha-2 receptors, such that vascular resistance increases. <br /> <br /> >Epinephrine is both a vasoconstrictor and vasodilator, depending on what receptors it attaches to. As a non-selective adrenergic agonist, it acts on Alpha-1, Alpha-2, Beta-1, Beta-2 and Beta-3 receptors that are found throughout the body's tissues, yielding many different physiological responses.<br /> <br /> ====Genes and Transcription Factors Involved with the Adrenal Medulla's Development====<br /> <br /> Members of the SOX (SRY-Box) gene family have multiple key contributors to Neural Crest in the Adrenal Medulla.<br /> <br /> Mouse models have demonstrated that SOX-10 knock-outs (mice whose DNA has been engineered to not express SOX-10) do not have an adrenal medulla. There has also been suggestion that SOX-8,9 and 10 are all strongly related to the migratory patterning of neural crest cells to the developing adrenal glands.<br /> <br /> The TH gene (for Tyrosine Hydroxylase) encodes the aforementioned enzyme in the adrenal medulla and central nervous system. Tyrosine Hydroxylase is crucial in biochemical pathways and cascades for the synthesis of catecholamines and other CNS neurotransmitters. The conversion from L-Tyrosine to L-DOPA is dependent upon the catalytic action of Tyrosine Hydroxylase. From there, L-DOPA can make Dopamine and eventually Epinephrine and Norepinephrine as well. <br /> <br /> [[File:Catecholamine_Synthesis.jpg|500px|thumb|right|Cascade of Catecholamine Synthesis]]<br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2291442/<br /> https://www.ncbi.nlm.nih.gov/pubmed/19396395<br /> <br /> ===Abnormalities/abnormal development===<br /> ----<br /> ===Animal models===<br /> ----<br /> Animal models are an integral part of research in embryology. In particular due to the moral concerns regarding the use of humans in scientific research. As a result different animals are used as substitutes to simulate the same environments and hope to achieve results that would also be able to represent humans as well. Prenatal adrenal gland development has been described in a number of scientific reports dating from the 1900s to studies in more recent years. These involved a variety of animal models such as ox, sheep, swine and most commonly mice. <br /> <br /> <br /> There has been extensive research conducted into the adrenal chromaffin cells and their embryological developments. As explained above nueral crest cells are pluripotent meaning they are able to differentiate into multiple different cells. The neural crest cells give rise to chromaffin cells of the adrenal medulla.<br /> Ahonen suggested that some neural crest cells continue migration from the chain ganglia to the lateral sides of aorta, where they form the perirenal ganglia and adrenal medulla, and finally to the ventral side of the aorta to form the preaortic sympathetic tissue. However, that report only showed the several transverse sections of the fetal trunk for the a demonstration of the migration route of neural crest cells. In this study, using three dimensional reconstructed images, we aimed to observe how TH-labeled chromaffin cells penetrate into the adrenal anlage to form the adrenal medulla and whether the migration route of TH - positive cells from the adrenal connects the preaortic sympathetic ganglia <br /> (M.Yamato, R. Yanai, K. Arishima, 2004) <br /> <br /> Prenatal adrenal gland development has been described in numerous published reports covering a wide variety of species, including the ox (Katznelson, 1966; Wrobel and Suss, 1999), sheep (Davies, 1950; Wintour et al., 1975; Upadhyay and Zamboni, 1982; Naaman‐Reperant and Durand, 1997; Grino, 2004), swine (Sokolov et al., 2006) and mouse (Waring, 1935; Ikeda et al., 1994; Sass, 1996; Nyska and Maronpot, 1999; Bland et al., 2003; Val et al., 2007). Adrenal gland development also has been extensively described for humans as well (Kolliker, 1879; Minot, 1892; Zuckerkandl, 1912; Wieman, 1920; Ikeda et al., 1981; Langlois et al., 2002; Hanley and Arit, 2006).<br /> <br /> https://www.sciencedirect.com/science/article/pii/S0925477302004550<br /> http://dev.biologists.org/content/develop/126/13/2935.full.pdf<br /> <br /> ===Current research (labs)===<br /> ----<br /> The findings presented until now have focused on the mechanisms controlling migration along the dorsolateral path. In comparison, our understanding of the mechanisms controlling NCC migration along the ventral path are complicated by the fact that this population comprises multiple precursors that form different derivatives in distinct regions of the embryo. For example, ventrally migrating NCCs either stop within the sclerotome in close association with the neural tube to form neurons and glia of the sensory nervous system (i.e. the dorsal root ganglia [DRG]), while other NCCs continue to migrate further ventrally to form the autonomic nervous system (i.e. sympathetic ganglia and chromaffin cells of the adrenal gland)<br /> <br /> Adrenomedullary chromaffin cells are catecholamine (CA)-producing cells originating from trunk neural crest (NC) via sympathoadrenal progenitors (SAPs). We generated NC and SAPs from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) in vitro via BMP2/FGF2 exposure, ascertained by qPCR and immunoexpression of SOX10, ASCL1, TFAP2α, and PHOX2B, and by fluorescence-activated cell sorting selection for p75NTR and GD2, and confirmed their trunk-like HOX gene expression. We showed that continuing BMP4 and curtailing FGF2 in vitro, augmented with corticosteroid mimetic, induced these cells to upregulate the chromaffin cell-specific marker PNMT and other CA synthesis and storage markers, and we demonstrated noradrenaline and adrenaline by Faglu and high-performance liquid chromatography. We showed these human cells' SAP-like property of migration and differentiation into cells expressing chromaffin cell markers by implanting them into avian embryos in vivo and in chorio-allantoic membrane grafts. These cells have the potential for investigating differentiation of human chromaffin cells and for modeling diseases involving this cell type.<br /> <br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768882/<br /> <br /> ===Glossary===<br /> ----<br /> ===Reference list===</div>

Z5091101 https://embryology.med.unsw.edu.au/embryology/index.php?title=2018_Group_Project_1&diff=355693 2018 Group Project 1 2018-10-07T07:28:41Z

<p>Z5091101: /* History */</p> <hr /> <div>=The Contribution of Neural Crest Cells to the Adrenal Medulla=<br /> ----<br /> {{2018ANAT2341ProjectHeader}}<br /> <br /> <br /> ===Introduction===<br /> [[User:Z5014972|Z5014972]] ([[User talk:Z5014972|talk]]) 12:47, 14 August 2018 (AEST)z5014972 <br /> good review article https://link.springer.com/article/10.1007%2Fs12022-009-9070-6<br /> ----<br /> ===History===<br /> ----<br /> '''Describing the neural crest'''<br /> [[File:Wilhelm_His_History_Wilhelm.jpeg|left|230px|thumb|Wilhelm His]]<br /> The "neural crest" is a structure in the embryo and is the junction between the neural and epidermal ectoderm. The neural crest contributes a large number of cells of varying structure and function that directly or indirectly contribute to the development of tissues and organs within the body {{#pmid:19179766|PMID19179766}}. In 1868, the neural crest cells were first identified in a chick embryo as a collection of cells known as "Zwischenstrang" by Professor Wilhelm His {{#pmid:22820859|PMID22820859}}. Wilhelm His was among the first to provide an explanation for the mechanics governing the developing embryo as well as the physiology and the organs that the differing germinal regions would eventually give rise to. In 1878, the term neural ridge was used to describe this collection of cells but the term neural crest was later coined by Arthur Milnes Marshall in 1879 in a paper he worked on disseminating the knowledge from his research on the development of cranial nerves in chicken embryos. {{#pmid:19179766|PMID19179766}}.<br /> [[File:NC Location.jpg|left|500px|thumb|The neural crest]]<br /> <br /> '''1890s-1950s'''<br /> The neural crest is the point of origin for spinal/cranial ganglia and neurons. This theory received little criticism and was not contested much by other researchers prior to the 1890s. This is owing to the fact that the neural crest is quite closely related to the neural tube and thus this relationship makes sense. This discovery was made by His and Marshall, however, they found this out independently of one another.In the 1890s, Julia Platt, claimed that odontoblasts as well as the cartilages forming the facial and pharyngeal arch skeletons came from the ectoderm. This created much debate and was contested by many. <br /> <br /> This is because this theory completely contradicted the germ-layer theory, whereby skeletal tissues originate at the mesoderm and not the ectoderm. The controversies this finding created brought about a slowing down of research, as demonstrated by a gap of almost 40 years between the theory that skeletal tissues originating from the neural crest. Today, it is known that the neural crest does indeed play a role in the development of the skeleton in vertebrates, particularly, the cranial neural crest. Although these studies were occurring, the focus was still primarily on researching pigment cells and ganglia of the spine up until the 1950s, when Sven Hörstadius' major work on the neural crest was published, titled "The Neural Crest: Its properties and derivatives in the light of experimental research". This work focused on experimental data tracing the development of the cartilaginous skeleton derived from the neural crest {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1960s - 1970s'''<br /> In the 1960s, the migration patterns of neural crest cells were studied in avian embryos (birds). This was a shift from studying the embryos of amphibians. This was inspired by studies conducted in the 1960s on neural crest cells migrating from the brain and spinal cord, known as trunk and cranial neural crest cells {{#pmid:19179766|PMID19179766}}. The cranial neural crest eventually becomes the bones, cartilage and connective tissues forming the foundation of the face, ears and teeth. The trunk neural crest cells can either become melanocytes or can migrate into sclerotomes which are later contributors to the cartilage of the spine and the dorsal root ganglia {{#pmid:22820859|PMID22820859}}. The cells in the trunk neural crest that migrate vertically become the sympathetic ganglia, the nerves proximal to the aorta and the adrenal medulla '''[W]'''. In the 1970s many detailed maps signifying the pathways of many of the neural crest cells appeared as well as an understanding that the environment in which the neural crest cells are found plays a major role in their final development as well as the occurrences of abnormalities in the fetus {{#pmid:19179766|PMID19179766}}.<br /> <br /> '''1980s - 21st century'''<br /> From the 1980s-1990s, the causative agent of organ transformation from one to another (homeotic patterning), as well as the Hox genes which regulate the axis of most symmetrical animal embryos were founded and studied. The neural crest, which previously was divided into the cranial and trunk regions, was now further divided into the vagal and sacral neural crest, the cardiac neural crest and the cephalic neural crest {{#pmid:19179766|PMID19179766}}. The vagal & sacral neural crest gives rise to the parasympathetic ganglia found in the gut. Without these ganglia, peristalsis, is not possible '''[W]'''. The cardiac neural crest contributes to the valves, septa and major blood vessels of the heart, as well as connective tissues and cartilage{{#pmid:19179766|PMID19179766}}. This is important for the structure of the heart as well as its overall function, enabling it to move blood around the body efficiently as well as keep pulmonary and aortic circulation separated '''[W]'''. <br /> <br /> Today, knowledge of the neural crest cells, their migration patterns, modes of differentiation, derivatives and apoptosis (cell death) are being studied extensively. This is being done on a comparative basis between different organisms, to add further evidence for evolution {{#pmid:19179766|PMID19179766}}. The neural crest is definitely forging a "crest" between the fields of developmental and evolutionary biology, as it is a structure '''shared exclusively by all vertebrates'''. Invertebrates do not derive their specialised cells from the neural crest as they do not have one, rather, they derive these from the endomesoderm {{#pmid:22230617|PMID22230617}}.<br /> <br /> [[File:Regions_of_NC_Cells.jpg|left|250px|thumb|Neural crest regions]]<br /> <br /> <br /> <br /> <br /> <br /> <br /> '''[W]''' - need to reference: https://www.ncbi.nlm.nih.gov/books/NBK10065/<br /> <br /> ===Embryonic origins===<br /> ----<br /> https://www.ncbi.nlm.nih.gov/books/NBK10065/<br /> <br /> ===Developmental time course===<br /> ----<br /> <br /> The adrenal gland has two distinct sections, the cortex and the medulla, both with different embryonic origins. The cortex accounts for 90% of the adrenal glands and arises from intermediate mesoderm. The medulla only accounts for 10% of the adult adrenal glands, however it has neural crest embryonic origin. The medulla consists of chromaffinoblast cells which are migrant neuroblast cells from the neural crest, therefore the adrenal medulla is a component of the sympathetic nervous system.{{#pmid:21175739|PMID21175739}} Neural crest cells replicate in week 7 and begin to differentiate in week 8, the cells then migrate to the developing adrenal gland in week 9 of development.{{#pmid:25255746|PMID25255746}}{{#pmid:18279781|PMID18279781}} The neural crest cells infiltrate the cortex and the chromaffin cells are scattered islands in the cortex.{{#pmid:23354096|PMID23354096}} Throughout development the cells will become more compact in the centre of the gland, during this period of development the adrenal gland is growing rapidly. The gland is abnormally large until the second trimester and the medulla is much thicker prenatally.{{#pmid:18279781|PMID18279781}}{{#pmid:21175739|PMID21175739}}<br /> <br /> ===Developmental/adult function===<br /> ----<br /> ===Tissue/organ structure===<br /> <br /> ====Normal Structure and Function of the Adrenal Medulla====<br /> <br /> The cells of the adrenal medulla are derived from the neural crest as opposed to the mesodermal origins of the cortex. The medulla contains secretory cells called chromaffin cells, due to the agents they produce when oxidised, such as chromate. These cells secrete epinephrine and norepinephrine in response to various substances such as acetylcholine.<br /> <br /> There are three types of cells in the adult adrenal medulla: <br /> 1) Epinephrine cells<br /> 2) Norepinephrine cells <br /> 3) Small granule-containing cells (SGCs)<br /> These cells also produce various other peptides such as substance P and neurotensin. The adrenal medulla also contains presynaptic sympathetic ganglion cells. <br /> <br /> <br /> ====Related Anatomy====<br /> <br /> The tissue and organ structure of the adrenal medulla should be understood with regard to its specialised function within the sympathetic nervous system. <br /> <br /> The medullary region of the adrenal glands is tasked with the endocrine secretions of adrenaline and nor-adrenaline in response to environmental stressors that are signalled for by the sympathetic nervous system. That is, the secretion of fight-or-flight response hormones in order to restrict vasculature to the trunk and increase vascular activity in the peripheral musculature.<br /> <br /> The adrenal glands are supplied by several branches of the great vessels in the abdominal cavity. The secreted catecholamines in the medulla are directly able to pass to the blood stream this way.<br /> <br /> These adrenal glands and their contents are retroperitoneal in the adult and varied in shape, with the left often being semilunar and right being pyramidal. Nervous supply of the adrenal glands is achieved by contributions from the splanchnic nerves of the celiac plexus. <br /> <br /> <br /> [[File:Dd.jpg|500px|thumb|right|Adult Adrenal Glands in situ]] <br /> ----<br /> <br /> ===Molecular mechanisms/factors/genes===<br /> ----<br /> <br /> ====Role of Adrenal Medulla in the Neonate and Adult====<br /> <br /> Understanding the biochemistry of catecholamines is necessary to see how the adrenal medulla is designed in the stages of embryology and how it is suited for life in the neonate and adult. <br /> <br /> The epinephrine and norepinephrine in the neonate and adult work by primarily changing the osmoregulatory state of vasculature in organs. With the exclusion of their neuromodulatory and neurotransmitter functions, epinephrine and norepinephrine are mainly tasked with the control of sympathetic and parasympathetic supplies. <br /> <br /> >Norepinephrine is a constrictor of peripheral vasculature by antagonising the action of surface receptors expressed on the endothelium of blood vessels, specifically Alpha-1 and Alpha-2 receptors, such that vascular resistance increases. <br /> <br /> >Epinephrine is both a vasoconstrictor and vasodilator, depending on what receptors it attaches to. As a non-selective adrenergic agonist, it acts on Alpha-1, Alpha-2, Beta-1, Beta-2 and Beta-3 receptors that are found throughout the body's tissues, yielding many different physiological responses.<br /> <br /> ====Genes and Transcription Factors Involved with the Adrenal Medulla's Development====<br /> <br /> Members of the SOX (SRY-Box) gene family have multiple key contributors to Neural Crest in the Adrenal Medulla.<br /> <br /> Mouse models have demonstrated that SOX-10 knock-outs (mice whose DNA has been engineered to not express SOX-10) do not have an adrenal medulla. There has also been suggestion that SOX-8,9 and 10 are all strongly related to the migratory patterning of neural crest cells to the developing adrenal glands.<br /> <br /> The TH gene (for Tyrosine Hydroxylase) encodes the aforementioned enzyme in the adrenal medulla and central nervous system. Tyrosine Hydroxylase is crucial in biochemical pathways and cascades for the synthesis of catecholamines and other CNS neurotransmitters. The conversion from L-Tyrosine to L-DOPA is dependent upon the catalytic action of Tyrosine Hydroxylase. From there, L-DOPA can make Dopamine and eventually Epinephrine and Norepinephrine as well. <br /> <br /> [[File:Catecholamine_Synthesis.jpg|500px|thumb|right|Cascade of Catecholamine Synthesis]]<br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2291442/<br /> https://www.ncbi.nlm.nih.gov/pubmed/19396395<br /> <br /> ===Abnormalities/abnormal development===<br /> ----<br /> ===Animal models===<br /> ----<br /> Animal models are an integral part of research in embryology. In particular due to the moral concerns regarding the use of humans in scientific research. As a result different animals are used as substitutes to simulate the same environments and hope to achieve results that would also be able to represent humans as well. Prenatal adrenal gland development has been described in a number of scientific reports dating from the 1900s to studies in more recent years. These involved a variety of animal models such as ox, sheep, swine and most commonly mice. <br /> <br /> <br /> There has been extensive research conducted into the adrenal chromaffin cells and their embryological developments. As explained above nueral crest cells are pluripotent meaning they are able to differentiate into multiple different cells. The neural crest cells give rise to chromaffin cells of the adrenal medulla.<br /> Ahonen suggested that some neural crest cells continue migration from the chain ganglia to the lateral sides of aorta, where they form the perirenal ganglia and adrenal medulla, and finally to the ventral side of the aorta to form the preaortic sympathetic tissue. However, that report only showed the several transverse sections of the fetal trunk for the a demonstration of the migration route of neural crest cells. In this study, using three dimensional reconstructed images, we aimed to observe how TH-labeled chromaffin cells penetrate into the adrenal anlage to form the adrenal medulla and whether the migration route of TH - positive cells from the adrenal connects the preaortic sympathetic ganglia <br /> (M.Yamato, R. Yanai, K. Arishima, 2004) <br /> <br /> Prenatal adrenal gland development has been described in numerous published reports covering a wide variety of species, including the ox (Katznelson, 1966; Wrobel and Suss, 1999), sheep (Davies, 1950; Wintour et al., 1975; Upadhyay and Zamboni, 1982; Naaman‐Reperant and Durand, 1997; Grino, 2004), swine (Sokolov et al., 2006) and mouse (Waring, 1935; Ikeda et al., 1994; Sass, 1996; Nyska and Maronpot, 1999; Bland et al., 2003; Val et al., 2007). Adrenal gland development also has been extensively described for humans as well (Kolliker, 1879; Minot, 1892; Zuckerkandl, 1912; Wieman, 1920; Ikeda et al., 1981; Langlois et al., 2002; Hanley and Arit, 2006).<br /> <br /> https://www.sciencedirect.com/science/article/pii/S0925477302004550<br /> http://dev.biologists.org/content/develop/126/13/2935.full.pdf<br /> <br /> ===Current research (labs)===<br /> ----<br /> The findings presented until now have focused on the mechanisms controlling migration along the dorsolateral path. In comparison, our understanding of the mechanisms controlling NCC migration along the ventral path are complicated by the fact that this population comprises multiple precursors that form different derivatives in distinct regions of the embryo. For example, ventrally migrating NCCs either stop within the sclerotome in close association with the neural tube to form neurons and glia of the sensory nervous system (i.e. the dorsal root ganglia [DRG]), while other NCCs continue to migrate further ventrally to form the autonomic nervous system (i.e. sympathetic ganglia and chromaffin cells of the adrenal gland)<br /> <br /> Adrenomedullary chromaffin cells are catecholamine (CA)-producing cells originating from trunk neural crest (NC) via sympathoadrenal progenitors (SAPs). We generated NC and SAPs from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) in vitro via BMP2/FGF2 exposure, ascertained by qPCR and immunoexpression of SOX10, ASCL1, TFAP2α, and PHOX2B, and by fluorescence-activated cell sorting selection for p75NTR and GD2, and confirmed their trunk-like HOX gene expression. We showed that continuing BMP4 and curtailing FGF2 in vitro, augmented with corticosteroid mimetic, induced these cells to upregulate the chromaffin cell-specific marker PNMT and other CA synthesis and storage markers, and we demonstrated noradrenaline and adrenaline by Faglu and high-performance liquid chromatography. We showed these human cells' SAP-like property of migration and differentiation into cells expressing chromaffin cell markers by implanting them into avian embryos in vivo and in chorio-allantoic membrane grafts. These cells have the potential for investigating differentiation of human chromaffin cells and for modeling diseases involving this cell type.<br /> <br /> <br /> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768882/<br /> <br /> ===Glossary===<br /> ----<br /> ===Reference list===</div>

Z5091101 https://embryology.med.unsw.edu.au/embryology/index.php?title=File:Regions_of_NC_Cells.jpg&diff=355691 File:Regions of NC Cells.jpg 2018-10-07T07:25:12Z

<p>Z5091101: This image shows the regions where the different neural crest cells can be found. Note how these regions were discovered initially as the trunk and cranial neural crest cells, but later the existence of sacral, vagal and cardiac neural crest cells was...</p> <hr /> <div>This image shows the regions where the different neural crest cells can be found. Note how these regions were discovered initially as the trunk and cranial neural crest cells, but later the existence of sacral, vagal and cardiac neural crest cells was confirmed. It is the cells that migrate vertically from the trunk neural crest that become the adrenal medulla. <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> This image was inspired by the figure 2 on the following page: https://jacobspublishers.com/molecular-mechanism-of-cranial-neural-crest-cell-development/</div>

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