Talk:Gastrointestinal Tract Development
|trachea, respiratory tract, lungs
gallbladder ( and bile ducts)
pancreas (dorsal & ventral)
small intestines (jejunum, ileum)
proximal 2/3 of transverse colon
|distal 1/3 of transverse colon
Upper anal canal
|celiac artery||superior mesenteric artery||inferior mesenteric artery|
- Historic Embryology: 1878 Alimentary Canal | 1882 The Organs of the Inner Germ-Layer The Alimentary Tube with its Appended Organs | 1902 The Organs of Digestion | 1907 Development of the Digestive System | 1907 Atlas | 1907 23 Somite Embryo | 1912 Digestive Tract | 1917 Entodermal Canal | 1918 Anatomy | 1921 Alimentary Tube
- 1908 13-14 Somite Embryo
- 1926 22 Somite Embryo
- 1907 23 Somite Embryo
- 1937 25 Somite Embryo
- 1914 27 Somite Embryo
- 1914 Week 7 Embryo
- Anatomy of the Human Body 1918 Henry Gray 2. The Digestive Apparatus
The Digestive Tract and Derived Primordia Differentiate by Following a Precise Timeline in Human Embryos Between Carnegie Stages 11 and 13
Anat Rec (Hoboken). 2016 Apr;299(4):439-49. doi: 10.1002/ar.23314. Epub 2016 Jan 30.
Ueno S1, Yamada S1,2, Uwabe C2, Männer J3, Shiraki N1, Takakuwa T1.
The precise mechanisms through which the digestive tract develops during the somite stage remain undefined. In this study, we examined the morphology and precise timeline of differentiation of digestive tract-derived primordia in human somite-stage embryos. We selected 37 human embryos at Carnegie Stage (CS) 11-CS13 (28-33 days after fertilization) and three-dimensionally analyzed the morphology and positioning of the digestive tract and derived primordia in all samples, using images reconstructed from histological serial sections. The digestive tract was initially formed by a narrowing of the yolk sac, and then several derived primordia such as the pharynx, lung, stomach, liver, and dorsal pancreas primordia differentiated during CS12 (21-29 somites) and CS13 (≥ 30 somites). The differentiation of four pairs of pharyngeal pouches was complete in all CS13 embryos. The respiratory primordium was recognized in ≥ 26-somite embryos and it flattened and then branched at CS13. The trachea formed and then elongated in ≥ 35-somite embryos. The stomach adopted a spindle shape in all ≥ 34-somite embryos, and the liver bud was recognized in ≥ 27-somite embryos. The dorsal pancreas appeared as definitive buddings in all but three CS13 embryos, and around these buddings, the small intestine bent in ≥ 33-somite embryos. In ≥ 35-somite embryos, the small intestine rotated around the cranial-caudal axis and had begun to form a primitive intestinal loop, which led to umbilical herniation. These data indicate that the digestive tract and derived primordia differentiate by following a precise timeline and exhibit limited individual variations. Anat Rec, 299:439-449, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc. KEYWORDS: derived primordial; development; digestive tract; human embryo; timeline
Potential Regulatory Role of MicroRNAs in the Development of Bovine Gastrointestinal Tract during Early Life
PLoS One. 2014 Mar 28;9(3):e92592. doi: 10.1371/journal.pone.0092592. eCollection 2014.
Liang G1, Malmuthuge N1, McFadden TB2, Bao H1, Griebel PJ3, Stothard P1, Guan LL1. Author information
Abstract This study aimed to investigate the potential regulatory role of miRNAs in the development of gastrointestinal tract (GIT) during the early life of dairy calves. Rumen and small intestinal (mid-jejunum and ileum) tissue samples were collected from newborn (30 min after birth; n = 3), 7-day-old (n = 6), 21-day-old (n = 6), and 42-day-old (n = 6) dairy calves. The miRNA profiling was performed using Illumina RNA-sequencing and the temporal and regional differentially expressed miRNAs were further validated using qRT-PCR. Analysis of 16S rRNA gene copy numbers was used to quantify total bacteria, Bifidobacterium and Lactobacillus species. The expression of miR-143 was abundant in all three gut regions, at all time points and it targets genes involved primarily in the proliferation of connective tissue cells and muscle cells, suggesting a role in regulating rapid tissue development during the early life of calves. The expression of miR-146, miR-191, miR-33, miR-7, miR-99/100, miR-486, miR-145, miR-196 and miR-211 displayed significant temporal differences (FDR <0.05), while miR-192/215, miR-194, miR-196, miR-205 and miR-31 revealed significant regional differences (FDR <0.05). The expression levels of miR-15/16, miR-29 and miR-196 were positively correlated with the copy numbers of 16S rRNA gene of Bifidobacterium or Lactobacillus species or both (P<0.05). Functional analysis using Ingenuity Pathway Analysis identified the above mentioned differentially expressed miRNAs as potential regulators of gut tissue cell proliferation and differentiation. The bacterial density-associated miRNAs were identified as modulators of the development of lymphoid tissues (miR-196), maturation of dendritic cells (miR-29) and development of immune cells (miR-15/16). The present study revealed temporal and regional changes in miRNA expression and a correlation between miRNA expression and microbial population in the GIT during the early life, which provides further evidence for another mechanism by which host-microbial interactions play a role in regulating gut development.
Endodermal Hedgehog signals modulate Notch pathway activity in the developing digestive tract mesenchyme
Development. 2011 Aug;138(15):3225-33.
Kim TH, Kim BM, Mao J, Rowan S, Shivdasani RA. Source Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
The digestive tract epithelium and its adjoining mesenchyme undergo coordinated patterning and growth during development. The signals they exchange in the process are not fully characterized but include ligands of the Hedgehog (Hh) family, which originate in the epithelium and are necessary for mesenchymal cells to expand in number and drive elongation of the developing gut tube. The Notch signaling pathway has known requirements in fetal and adult intestinal epithelial progenitors. We detected Notch pathway activity in the embryonic gut mesenchyme and used conditional knockout mice to study its function. Selective disruption of the Notch effector gene RBP-Jκ (Rbpj) in the mesenchyme caused progressive loss of subepithelial fibroblasts and abbreviated gut length, revealing an unexpected requirement in this compartment. Surprisingly, constitutive Notch activity also induced rapid mesenchymal cell loss and impaired organogenesis, probably resulting from increased cell death and suggesting the need for a delicate balance in Notch signaling. Because digestive tract anomalies in mouse embryos with excess Notch activity phenocopy the absence of Hh signaling, we postulated that endodermal Hh restrains mesenchymal Notch pathway activity. Indeed, Hh-deficient embryos showed Notch overactivity in their defective gut mesenchyme and exposure to recombinant sonic hedgehog could override Notch-induced death of cultured fetal gut mesenchymal cells. These results reveal unexpected interactions between prominent signals in gastrointestinal development and provide a coherent explanation for Hh requirements in mesenchymal cell survival and organ growth.
The emergence of neural activity and its role in the development of the enteric nervous system
Dev Biol. 2013 Oct 1;382(1):365-74. doi: 10.1016/j.ydbio.2012.12.006. Epub 2012 Dec 19.
Hao MM1, Bornstein JC, Vanden Berghe P, Lomax AE, Young HM, Foong JP. Author information Abstract The enteric nervous system (ENS) is a vital part of the autonomic nervous system that regulates many gastrointestinal functions, including motility and secretion. All neurons and glia of the ENS arise from neural crest-derived cells that migrate into the gastrointestinal tract during embryonic development. It has been known for many years that a subpopulation of the enteric neural crest-derived cells expresses pan-neuronal markers at early stages of ENS development. Recent studies have demonstrated that some enteric neurons exhibit electrical activity from as early as E11.5 in the mouse, with further maturation of activity during embryonic and postnatal development. This article discusses the maturation of electrophysiological and morphological properties of enteric neurons, the formation of synapses and synaptic activity, and the influence of neural activity on ENS development. KEYWORDS: Enteric nervous system; Neural activity development; Neuron differentiation; Synapse formation PMID: 23261929 DOI: 10.1016/j.ydbio.2012.12.006
Early morphogenesis of ciliated cells in human oral cavity
Ontogenez. 2013 Nov-Dec;44(6):389-95.
[Article in Russian] Kurtova AI, Chernikov VP, Savel'ev SV.
Ciliated cells were found in the epithelium of the oral cavity of human embryos and fetuses starting from the seventh week of prenatal development. At the early stages of prenatal development (until the 13th week), cells with cilia cover most of the dorsal surface of the tongue and the soft palate, whereas they are found only near the gland ducts in the circumvallate and foliate lingual papillae after 17 weeks of development. The ultrastructure of the axoneme of cilia corresponds to the structure of motile cilia and is represented by nine microtubule doublets that surround the central pair of microtubule singlets. An immunohistochemical study performed on weeks 10-12 of development identified nerve endings associated with the ciliated cells. Until the 14th week of development, the cytoplasm of ciliated cells is immunopositive for NSE. The spatial distribution of ciliated cells in the tongue epithelium until the 13th week of development is not related to the morphogenesis of lingual papillae, and their role in the human oral cavity during the first trimester of pregnancy is unclear and requires further study.
Salivary gland branching morphogenesis--recent progress and future opportunities
Int J Oral Sci. 2010 Sep;2(3):117-26.
Hsu JC, Yamada KM. Source Laboratory of Cell and Developmental Biology, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892-4370, USA. Abstract Salivary glands provide saliva to maintain oral health, and a loss of salivary gland function substantially decreases quality-of-life. Understanding the biological mechanisms that generate salivary glands during embryonic development may identify novel ways to regenerate function or design artificial salivary glands. This review article summarizes current research on the process of branching morphogenesis of salivary glands, which creates gland structure during development. We highlight exciting new advances and opportunities in studies of cell-cell interactions, mechanical forces, growth factors, and gene expression patterns to improve our understanding of this important process.
Different thymosin Beta 4 immunoreactivity in foetal and adult gastrointestinal tract
PLoS One. 2010 Feb 9;5(2):e9111.
Nemolato S, Cabras T, Cau F, Fanari MU, Fanni D, Manconi B, Messana I, Castagnola M, Faa G.
Divisione di Anatomia Patologica, Dipartimento di Citomorfologia, University of Cagliari, Cagliari, Italy. Abstract BACKGROUND: Thymosin beta 4 (Tbeta(4)) is a member of beta-thymosins, a family of peptides that play essential roles in many cellular functions. A recent study from our group suggested a role for Tbeta(4) in the development of human salivary glands. The aim of this study was to analyze the expression of Tbeta(4) in the human gut during development, and in the adult.
METHODOLOGY/PRINCIPAL FINDINGS: Immunolocalization of Tbeta(4) was studied in autoptic samples of tongue, oesophagus, stomach, ileum, colon, liver and pancreas obtained from two human foetuses and two adults. Tbeta(4) appeared unevenly distributed, with marked differences between foetuses and adults. In the stomach, superficial epithelium was positive in foetuses and negative in adults. Ileal enterocytes were strongly positive in the adult and weakly positive in the foetuses. An increase in reactivity for Tbeta(4) was observed in superficial colon epithelium of adults as compared with the foetuses. Striking differences were found between foetal and adult liver: the former showed a very low reactivity for Tbeta(4) while in the adult we observed a strong reactivity in the vast majority of the hepatocytes. A peculiar pattern was found in the pancreas, with the strongest reactivity observed in foetal and adult islet cells.
SIGNIFICANCE: Our data show a strong expression of Tbeta(4) in the human gut and in endocrine pancreas during development. The observed differential expression of Tbeta(4) suggests specific roles of the peptide in the gut of foetuses and adults. The observed heterogeneity of Tbeta(4) expression in the foetal life, ranging from a very rare detection in liver cells up to a diffuse reactivity in endocrine pancreas, should be taken into account when the role of Tbeta(4) in the development of human embryo is assessed. Future studies are needed to shed light on the link between Tbeta(4) and organogenesis.
TGF-β2 Suppresses Macrophage Cytokine Production and Mucosal Inflammatory Responses in the Developing Intestine
Maheshwari A, Kelly DR, Nicola T, Ambalavanan N, Jain SK, Murphy-Ullrich J, Athar M, Shimamura M, Bhandari V, Aprahamian C, Dimmitt RA, Serra R, Ohls RK. Gastroenterology. 2010 Sep 24. [Epub ahead of print] PMID 20875417
"Premature neonates born before 32 weeks of gestation or with a birth weight <1500 grams are predisposed to necrotizing enterocolitis (NEC), an idiopathic, inflammatory bowel necrosis characterized by pneumatosis intestinalis (accumulation of gaseous products of bacterial fermentation within the bowel wall)"
"occurrence of NEC only after postnatal bacterial colonization and never in the sterile intrauterine microenvironment prior to birth"
"NEC is believed to occur when mucosal injury or altered permeability in the preterm intestine permits the translocation of luminal bacteria across the epithelial barrier, which, in turn, triggers a severe inflammatory response"
Left-right asymmetry in gut development: what happens next?
Bioessays. 2009 Oct;31(10):1026-37. Burn SF, Hill RE. Source MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK. Abstract The gastrointestinal tract is an asymmetrically patterned organ system. The signals which initiate left-right asymmetry in the developing embryo have been extensively studied, but the downstream steps required to confer asymmetric morphogenesis on the gut organ primordia are less well understood. In this paper we outline key findings on the tissue mechanics underlying gut asymmetry, across a range of species, and use these to synthesise a conserved model for asymmetric gut morphogenesis. We also discuss the importance of correct establishment of left-right asymmetry for gut development and the consequences of perturbations in this process.
The role of the visceral mesoderm in the development of the gastrointestinal tract
Gastroenterology. 2009 Jun;136(7):2074-91. Epub 2009 Mar 17.
McLin VA, Henning SJ, Jamrich M. Source Department of Pediatrics, Section of Gastroenterology, Hepatology and Nutrition, Baylor College of Medicine, Houston, Texas, USA. email@example.com Abstract The gastrointestinal (GI) tract forms from the endoderm (which gives rise to the epithelium) and the mesoderm (which develops into the smooth muscle layer, the mesenchyme, and numerous other cell types). Much of what is known of GI development has been learned from studies of the endoderm and its derivatives, because of the importance of epithelial biology in understanding and treating human diseases. Although the necessity of epithelial-mesenchymal cross talk for GI development is uncontested, the role of the mesoderm remains comparatively less well understood. The transformation of the visceral mesoderm during development is remarkable; it differentiates from a very thin layer of cells into a complex tissue comprising smooth muscle cells, myofibroblasts, neurons, immune cells, endothelial cells, lymphatics, and extracellular matrix molecules, all contributing to the form and function of the digestive system. Understanding the molecular processes that govern the development of these cell types and elucidating their respective contribution to GI patterning could offer insight into the mechanisms that regulate cell fate decisions in the intestine, which has the unique property of rapid cell renewal for the maintenance of epithelial integrity. In reviewing evidence from both mammalian and nonmammalian models, we reveal the important role of the visceral mesoderm in the ontogeny of the GI tract.
The serosal mesothelium is a major source of smooth muscle cells of the gut vasculature.
Wilm B, Ipenberg A, Hastie ND, Burch JB, Bader DM.
Most internal organs are situated in a coelomic cavity and are covered by a mesothelium. During heart development, epicardial cells (a mesothelium) move to and over the heart, undergo epithelial-mesenchymal transition (EMT), and subsequently differentiate into endothelial and vascular smooth muscle cells. This is thought to be a unique process in blood vessel formation. Still, structural and developmental similarities between the heart and gut led us to test the hypothesis that a conserved or related mechanism may regulate blood vessel development to the gut, which, similar to the heart, is housed in a coelomic cavity. By using a combination of molecular genetics, vital dye fate mapping, organ culture and immunohistochemistry, we demonstrate that the serosal mesothelium is the major source of vasculogenic cells in developing mouse gut. Our studies show that the gut is initially devoid of a mesothelium but that serosal mesothelial cells expressing the Wilm's tumor protein (Wt1) move to and over the gut. Subsequently, a subset of these cells undergoes EMT and migrates throughout the gut. Using Wt1-Cre genetic lineage marking of serosal cells and their progeny, we demonstrate that these cells differentiate to smooth muscle of all major blood vessels in the mesenteries and gut. Our data reveal a conserved mechanism in blood vessel formation to coelomic organs, and have major implications for our understanding of vertebrate organogenesis and vascular deficiencies of the gut.
Pancreas cell fate
- "Diabetes is characterized by decreased function of insulin-producing beta cells and insufficient insulin output resulting from an absolute (Type 1) or relative (Type 2) inadequate functional beta cell mass. Both forms of the disease would greatly benefit from treatment strategies that could enhance beta cell regeneration and/or function. Successful and reliable methods of generating beta cells or whole islets from progenitor cells in vivo or in vitro could lead to restoration of beta cell mass in individuals with Type 1 diabetes and enhanced beta cell compensation in Type 2 patients. A thorough understanding of the normal developmental processes that occur during pancreatic organogenesis, for example, transcription factors, cell signaling molecules, and cell-cell interactions that regulate endocrine differentiation from the embryonic pancreatic epithelium, is required in order to successfully reach these goals. This review summarizes our current understanding of pancreas development, with particular emphasis on factors intrinsic or extrinsic to the pancreatic epithelium that are involved in regulating the development and differentiation of the various pancreatic cell types. We also discuss the recent progress in generating insulin-producing cells from progenitor sources."
Salivary gland branching morphogenesis: a quantitative systems analysis of the Eda/Edar/NFkappaB paradigm
BMC Dev Biol. 2009 Jun 6;9:32.
Melnick M, Phair RD, Lapidot SA, Jaskoll T. Source Laboratory for Developmental Genetics, USC, Los Angeles, CA, USA. firstname.lastname@example.org
BACKGROUND: Ectodysplasin-A appears to be a critical component of branching morphogenesis. Mutations in mouse Eda or human EDA are associated with absent or hypoplastic sweat glands, sebaceous glands, lacrimal glands, salivary glands (SMGs), mammary glands and/or nipples, and mucous glands of the bronchial, esophageal and colonic mucosa. In this study, we utilized EdaTa (Tabby) mutant mice to investigate how a marked reduction in functional Eda propagates with time through a defined genetic subcircuit and to test the proposition that canonical NFkappaB signaling is sufficient to account for the differential expression of developmentally regulated genes in the context of Eda polymorphism.
RESULTS: The quantitative systems analyses do not support the stated hypothesis. For most NFkappaB-regulated genes, the observed time course of gene expression is nearly unchanged in Tabby (EdaTa) as compared to wildtype mice, as is NFkappaB itself. Importantly, a subset of genes is dramatically differentially expressed in Tabby (Edar, Fgf8, Shh, Egf, Tgfa, Egfr), strongly suggesting the existence of an alternative Eda-mediated transcriptional pathway pivotal for SMG ontogeny. Experimental and in silico investigations have identified C/EBPalpha as a promising candidate.
CONCLUSION: In Tabby SMGs, upregulation of the Egf/Tgfalpha/Egfr pathway appears to mitigate the potentially severe abnormal phenotype predicted by the downregulation of Fgf8 and Shh. Others have suggested that the buffering of the phenotypic outcome that is coincident with variant Eda signaling could be a common mechanism that permits viable and diverse phenotypes, normal and abnormal. Our results support this proposition. Further, if branching epithelia use variations of a canonical developmental program, our results are likely applicable to understanding the phenotypes of other branching organs affected by Eda (EDA) mutation.
Embryonic development of the ganglion plexuses and the concentric layer structure of human gut: a topographical study
Anat Embryol (Berl). 2004 Apr;208(1):33-41. Epub 2004 Feb 27.
Fu M1, Tam PK, Sham MH, Lui VC.
In this study, we performed a detailed topographical study on the development of ganglion plexuses and the smooth muscle layers of human embryonic and fetal gut. Neuron and glia differentiation was investigated with anti-PGP9.5 and anti-S100 antibodies respectively. The differentiation of smooth muscle and interstitial cells of Cajal (ICC) was studied with anti-smooth muscle alpha-actin and anti-C-Kit antibodies respectively. By week 7, rostro-caudal neural crest cell (NCC) colonization of the gut was complete, and NCCs have differentiated into neurons and glia. At the foregut, neurons and glia were aggregated into ganglion plexus in the myenteric region, and the longitudinal and circular muscle layers have started to differentiate; however, neurons and glia were not found in the submucosa. At the hindgut, neurons and glia were dispersed within the mesenchyme. Myenteric plexus, longitudinal and circular muscle layers formed along the entire gut by week 9. Scattered and individual neurons and glia, and small ganglion plexuses were detected in the foregut and midgut submucosa by week 12. Ganglion plexus was not seen in the hindgut submucosa until week 14. Muscularis mucosae was formed at the foregut and midgut by week 12 but was only discernible at the hindgut 2 weeks later. As the gut wall developed, ganglion plexus increased in size with more neurons and glia, and the formation of intra-plexus nerve fascicle. ICCs were localized in the ganglion plexus as early as week 7. ICCs were initially dispersed in the plexus and were preferentially localized at the periphery of the plexus by week 20. The specification of the annular layers of human embryonic and fetal gut follows a strict spatio-temporal pattern in a rostro-caudal and centripetal manner suggesting that interaction between (1) homotypic and/or heterotypic cells; and (2) cells and the extracellular matrix is critical for the embryonic development of the gut mesenchyme and the enteric nervous system.
PMID 14991401 DOI: 10.1007/s00429-003-0371-0
Morphological studies of the developing human esophageal epithelium
Microsc Res Tech. 1995 Jun 15;31(3):215-25. Ménard D. Source Département d'Anatomie et de Biologie Cellulaire, Faculté de Médecine, Université de Sherbrooke, Québec, Canada.
This article focusses on the structural development of human esophageal ciliated epithelium. A combination of transmission electron microscopic (TEM), scanning electron microscopic (SEM), radioautographic, and light microscopic (LM) analyses were carried out using intact fetal tissues between 8 and 20 weeks of gestation as well as cultured esophageal explants. Up to the age of 10 weeks, the stratified esophageal epithelium consisted of two longitudinal primary folds. The surface cells were undifferentiated and contained large glycogen aggregates. Between 11 and 16 weeks, the primary folds (now up to four) had developed secondary folds. The thickness of the epithelium drastically increased (123%) in concomittance with a differentiation of surface columnar ciliated cells. These highly specialized surface cells exhibited junctional complexes and well-developed organelles with numerous microvilli interspersed among the cilia. Transverse sections revealed the internal structure of the cilia with a consistent pattern of nine doublet microtubules surrounding a central pair of single microtubules. Freeze-fracture studies illustrated the presence of a ciliary necklace composed of 6 ring-like rows of intramembranous particles. They also revealed the structure of ciliary cell tight junctions consisting of up to nine anastomosing strands (P-face) or complementary grooves (E-face). Ultrastructural studies (LM, TEM, SEM) of the esophageal squamous epithelium obtained after 15 days of culture showed that the newly formed epithelium was similar to adult human epithelium. Finally LM and SEM observations established that the esophagogastric junction was not yet well delineated, consisting of a transitional area composed of a mixture of esophageal ciliated cells and gastric columnar mucous cells.
Self Assessment Questions
- What is a pharyngeal arch and pouch? List the muscle, arch cartilage and nerves of each arch. List the derivatives of each pharyngeal pouch.
- Describe the main steps in the development of the tongue.
- What are the derivatives of the fore-, mid- and hind-gut?
- What is the buccopharyngeal membrane?
- How does the thyroid gland develop?
- Describe the normal development of the face and palate. List the major malformations of this region and their possible causes.
- How is the liver developed?
- What are the main processes involved in the elongation and rotation of the stomach and intestinal region?
- Describe the development of the pancreas.
- How does the myenteric plexus develop?
- List the basic principles in the development of the peritoneum.
- What are the functions of the liver and pancreas in the fetus? Does the gastro-intestinal tract function in the fetus?
- What are the consequences of malrotation of the gut?