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Neural Development Journal - https://neuraldevelopment.biomedcentral.com


=Ectoderm Development=
Draft page - [[Neural System - Molecular]]
[[Image:Stage10 neural sm.jpg|400px|right]]
[[Image:Stage10 SEM1.jpg|300px|right]]
== Introduction ==
This lecture will cover the early development of the ectoderm layer of the trilaminar embryo. Note that we will be returning later to discuss neural (central nervous system; brain and spinal cord) and neural crest (peripheral nervous system; sensory and sympathetic ganglia). Epidermis (integumentary, skin contribution) development will be briefly mentioned due to its ectoderm origin, but will also be covered later in the current course.


==2020==
{{#pmid:32375049}}


* '''Lectopia Lecture Audio''' Lecture Date: 11-08-2009 Lecture Time: 12:00 Venue: BioMed E Speaker: Mark Hill [http://lectopia.elearning.unsw.edu.au/ilectures/ilectures.lasso?ut=153&id=48837 Ectoderm]
'''Variation of Human Neural Stem Cells Generating Organizer States In Vitro before Committing to Cortical Excitatory or Inhibitory Neuronal Fates'''


==Lecture Objectives==
Better understanding of the progression of neural stem cells (NSCs) in the developing cerebral cortex is important for modeling neurogenesis and defining the pathogenesis of neuropsychiatric disorders. Here, we use RNA sequencing, cell imaging, and lineage tracing of mouse and human in vitro NSCs and monkey brain sections to model the generation of cortical neuronal fates. We show that conserved signaling mechanisms regulate the acute transition from proliferative NSCs to committed glutamatergic excitatory neurons. As human telencephalic NSCs develop from pluripotency in vitro, they transition through organizer states that spatially pattern the cortex before generating glutamatergic precursor fates. NSCs derived from multiple human pluripotent lines vary in these early patterning states, leading differentially to dorsal or ventral telencephalic fates. This work furthers systematic analyses of the earliest patterning events that generate the major neuronal trajectories of the human telencephalon.
* Understanding of events during the third and fourth week of development
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
* Understanding the process of notochord formation
KEYWORDS:
* Understanding the process of early neural development
BMP; EGFR; FGF2; brain organizer; glutamatergic neurons; human iPSC variation; inhibitory neurons; neural stem cell; neural transcriptional dynamics; neurogenesis; neuronal trajectory variation; patterning of the cortex
* Brief understanding of neural crest formation
PMID: 32375049 DOI: 10.1016/j.celrep.2020.107599
* Brief understanding of epidermis formation
* Understanding of the adult components derived from ectoderm
* Brief understanding of early neural abnormalities


==Textbook References==


* Human Embryology (3rd ed.) Chapter 5 p107-125
===UNSW Embryology Links===
* The Developing Human: Clinically Oriented Embryology (6th ed.)
* '''Ectoderm Lectures''' [[2010_Lecture_6|Early Neural Lecture 2010]] | [[2009_Lecture_6|Early Neural Lecture 2009]] | [http://embryology.med.unsw.edu.au/Science/ANAT2341lecture05.htm Neural Lecture 5 2008]
* '''Ectoderm Movies''' [[Flash_Movies#Neural|Neural Animations]] | [[Development_Animation_-_Notochord|Notochord]] | [[Movie_-_Central_Nervous_System_3D_stage_13|Stage 13 Embryo]] | [[Movie_-_Central_Nervous_System_3D_stage_22|Stage 22 Neural]] |
* '''Ectoderm Notes''' [[Week_3|Timeline - Embryonic Week 3]] | [[Embryonic_Development|Carnegie Stages]] | [[Neural System - Abnormalities]] | [http://embryology.med.unsw.edu.au/Notes/neuron.htm original Neural Notes] | [http://embryology.med.unsw.edu.au/Notes/ncrest.htm original Neural Crest Notes]


Other textbooks
* Animal Neural Development - A number of different animal models of neural development, both normal and abnormal, have been established. [[Mouse_Development#Neural_Development|Mouse]] | [[Pig_Development#Neural_Development|Pig]] | [[Rabbit_Development#Neural_Development|Rabbit]]


* Moore and Persaud Chapter 18 p451-489
* Essentials of Human Embryology Larson Chapter 5 p69-79
* Before We Are Born (5th ed.) Moore and Persaud Chapter 19 p423-458


==UNSW Embryology Links==
brain museum - histology images from different species http://www.brainmuseum.org/Specimens/index.html


* '''Ectoderm Slides''' [http://embryology.med.unsw.edu.au/Science/ANAT2341lecture05.htm Neural Lecture 5 2008] | [http://embryology.med.unsw.edu.au/pdf/ANAT2341L5Neurals1.pdf Neural Lecture 2008 - 1 slide/page ] | [http://embryology.med.unsw.edu.au/pdf/ANAT2341L5Neurals4.pdf Neural 2008 Slides - 4 slides/page] | [http://embryology.med.unsw.edu.au/pdf/ANAT2341L5Neurals6.pdf Neural Lecture 2008 Slides - 6 slides/page]
==Human Central Nervous System Development==
* '''Ectoderm Movies''' [http://embryology.med.unsw.edu.au/Movies/larsen/notoch.mov  Notochord] | [http://embryology.med.unsw.edu.au/Movies/larsen/noto.mov  Notochord] | [http://embryology.med.unsw.edu.au/Movies/larsen/neuralplt.mov  Neural Plate] | [http://embryology.med.unsw.edu.au/Movies/larsen/neurul.mov  Neurulation] | [http://embryology.med.unsw.edu.au/Movies/larsen/2neuro.mov  Secondary Neurulation]
* '''Ectoderm Notes''' [[Week_3|Timeline - Embryonic Week 3]] | [[Embryonic_Development|Carnegie Stages]] | [http://embryology.med.unsw.edu.au/wwwhuman/Stages/Stagesem.htm|Carnegie Stages - scanning electron micrographs] | [http://embryology.med.unsw.edu.au/Notes/neuron.htm Neural Notes] | [http://embryology.med.unsw.edu.au/Notes/ncrest.htm Neural Crest Notes] | [http://embryology.med.unsw.edu.au/Notes/neuron2.htm Neural Abnormalities] | [http://embryology.med.unsw.edu.au/Notes/skin.htm Integumentary Development] | [http://embryology.med.unsw.edu.au/Defect/page5e.htm Folic Acid and Neural Tube Defects] | [http://embryology.med.unsw.edu.au/Notes/week3.htm Week 3] |


== Development Overview ==
Joseph Altman and  Shirley A. Bayer


===Notochord===
http://neurondevelopment.org
[http://embryology.med.unsw.edu.au/Movies/larsen/notoch.mov  Movie - Notochord] | [http://embryology.med.unsw.edu.au/Movies/larsen/noto.mov  Movie - Notochord 2]
* forms initially as the Axial Process, a hollow tube which extends from the primitive pit , cranially to the oral membrane
* the axial process then allow transient communication between the amnion and the yolk sac through the neuroenteric canal.
* the axial process then merges with the Endodermal layer to form the Notochordal Plate.
* the notochordal plate then rises back into the Mesodermal layer as a solid column of cells which is the Notochord.  


===Ectoderm===
http://neurondevelopment.org


* 2 parts
===Atlas of Human Central Nervous System Development===
* midline neural plate
* The Spinal Cord from Gestational Week 4 to the 4th Postnatal Month
** columnar
Shirley A . Bayer and Joseph Altman
* lateral surface ectoderm
CRC Press 2002
** cuboidal
Print ISBN: 978-0-8493-1420-9
** sensory placodes
eBook ISBN: 978-1-4200-4018-0 http://www.crcnetbase.com/doi/book/10.1201/9781420040180
** epidermis of skin, hair, glands, anterior pituitary, teeth enamel
* The Human Brain During the Third Trimester
Shirley A . Bayer and Joseph Altman
CRC Press 2003
Print ISBN: 978-0-8493-1421-6
eBook ISBN: 978-0-203-49494-3 http://www.crcnetbase.com/doi/book/10.1201/9780203494943
* The Human Brain During the Second Trimester
Shirley A . Bayer and Joseph Altman
CRC Press 2005
Print ISBN: 978-0-8493-1422-3
eBook ISBN: 978-0-203-50748-3 http://www.crcnetbase.com/doi/book/10.1201/9780203507483
* The Human Brain During the Late First Trimester
Shirley A . Bayer and Joseph Altman
CRC Press 2006
Print ISBN: 978-0-8493-1423-0
eBook ISBN: 978-1-4200-0327-7 http://www.crcnetbase.com/doi/book/10.1201/9781420003277
*The Human Brain During the Early First Trimester
Shirley A . Bayer and Joseph Altman
CRC Press 2007
Print ISBN: 978-0-8493-1424-7
eBook ISBN: 978-1-4200-0328-4 http://www.crcnetbase.com/doi/book/10.1201/9781420003284


===Neural Plate===
==2019==
[[Image:Neural_plate_movie_icon.jpg|right]]
[[Image:Neuralplate cartoon.png|right]]
[[Image:Stage11 SEM1.jpg|thumb|Stage 11 neural groove to tube]]


[http://embryology.med.unsw.edu.au/Movies/larsen/neuralplt.mov  Movie - Neural Plate]
{{#pmid:31495570}}
* extends from buccopharyngeal membrane to primitive node
* forms above notochord and paraxial mesoderm
* neuroectodermal cells
** broad brain plate
** narrower spinal cord
* 3 components form: floor plate, neural plate, neural crest


'''Neural Determination'''- neuronal populations are specified before plate folds
During neural tube closure and spinal cord development, many cells die in both the central and peripheral nervous systems (CNS and PNS, respectively). However, myeloid-derived professional phagocytes have not yet colonized the trunk region during early neurogenesis. How apoptotic cells are removed from this region during these stages remains largely unknown. Using live imaging in zebrafish, we demonstrate that neural crest cells (NCCs) respond rapidly to dying cells and phagocytose cellular debris around the neural tube. Additionally, NCCs have the ability to enter the CNS through motor exit point transition zones and clear debris in the spinal cord. Surprisingly, NCCs phagocytosis mechanistically resembles macrophage phagocytosis and their recruitment toward cellular debris is mediated by interleukin-1β. Taken together, our results reveal a role for NCCs in phagocytosis of debris in the developing nervous system before the presence of professional phagocytes.
* signals from notochord and mesoderm - secrete noggin, chordin,follistatin
** all factors bind BMP-4 an inhibitor of neuralation
** bone morphogenic protein acts through membrane receptor
* lateral inhibition generates at spinal cord level 3 strips of cells
* expression of delta inhibits nearby cells, which express notch receptor, from becoming neurons
* Delta-Notch inetraction- generates Neural strips


===Neural Groove===
{{#pmid:31175213}}
[http://embryology.med.unsw.edu.au/Movies/larsen/neurul.mov  Movie - Neurulation]
{{neural}} {{fly}}
* forms in the midline of the neural plate (day 18-19)
* '''N-cadherin orchestrates self-organization of neurons within a columnar unit in the Drosophila medulla''' "The columnar structure is a basic unit of the brain, but its developmental mechanism remains unknown. The medulla, the largest ganglion of the fly visual center, provides a unique opportunity to reveal the mechanisms of three-dimensional organization of the columns. We reveal that column formation is initiated by three core neurons that establish distinct concentric domains within a column. We demonstrate the in vivo evidence of N-cadherin-dependent differential adhesion among the core columnar neurons within a column along a two-dimensional layer in the larval medulla. The two-dimensional larval columns evolve to form three distinct layers in the pupal medulla. We propose the presence of mutual interactions among the three layers during formation of the three-dimensional structures of the medulla columns." {{Neural}}
* either side of which are the neural folds which continues to deepen until about week 4
==2018==
* neural folds begins to fuse, beginning at 4th somite level


===Neural Tube===
===Caspases and matrix metalloproteases facilitate collective behavior of non-neural ectoderm after hindbrain neuropore closure===
[[Image:Stage12 SEM3.jpg|thumb|Stage 12 caudal neuropore]]
BMC Dev Biol. 2018 Jul 31;18(1):17. doi: 10.1186/s12861-018-0175-3.
* the neural tube forms the brain and spinal cord
* fusion of neural groove extends rostrally and caudally
* begins at the level of 4th somite
* closes neural groove "zips up" in some species.
** humans appear to close at multiple points along the tube.
* leaves 2 openings at either end - '''Neuropores'''
** cranial neuropore closes before caudal


Failure for the neural tube to close correctly or completely results in a '''neural tube defect'''.
Shinotsuka N1, Yamaguchi Y2,3, Nakazato K4, Matsumoto Y1, Mochizuki A4,5, Miura M6.


===Secondary Neuralation===
Abstract
[http://embryology.med.unsw.edu.au/Movies/larsen/2neuro.mov  Movie - Secondary Neurulation]
BACKGROUND:
* caudal end of neural tube formed by secondary neuralation
Mammalian brain is formed through neural tube closure (NTC), wherein both ridges of opposing neural folds are fused in the midline and remodeled in the roof plate of the neural tube and overlying non-neural ectodermal layer. Apoptosis is widely observed from the beginning of NTC at the neural ridges and is crucial for the proper progression of NTC, but its role after the closure remains less clear.
* develops from primitive streak region
* solid cord canalized by extension of neural canal
* mesodermal caudal eminence


==Neural Crest==
RESULTS:
[http://embryology.med.unsw.edu.au/Notes/ncrest.htm Neural Crest Notes]
Here, we conducted live-imaging analysis of the mid-hindbrain neuropore (MHNP) closure and revealed unexpected collective behavior of cells surrounding the MHNP. The cells first gathered to the closing point and subsequently relocated as if they were released from the point. Inhibition of caspases or matrix metalloproteases with chemical inhibitors impaired the cell relocation.
* a population of cells at the edge of the neural plate that lie dorsally when the neural tube fuses
** dorsal to the neural tube, as a pair of streaks
** pluripotential, forms many different types of cells
** cells migrate throughout the embryo
** studied by quail-chick chimeras
** transplanted quail cells have obvious nucleoli compared with chicken


===Neural Crest Derivitives===
CONCLUSIONS:
* dorsal root ganglia
These lines of evidence suggest that apoptosis-mediated degradation of extracellular matrix might facilitate the final process of neuropore closure.
* autonomic ganglia
* adrenal medulla
* drg sheath cells, glia
* pia-arachnoid sheath
* skin melanocytes
* connective tissue of cardiac outflow
* thyroid parafollicular cells
* craniofacial skeleton
* teeth odontoblasts


==Early Brain Structure==
KEYWORDS:
===Primary Vesicles===
Apoptosis; Caspases; Live-imaging; Matrix metalloproteases; Neural tube closure
[[Image:CNS primary vesicles.jpg]]
PMID: 30064364 PMCID: PMC6069860 DOI: 10.1186/s12861-018-0175-3
* rostral neural tube forms 3 primary brain vesicles (week 4)
* 3 primary vesicles: '''prosencephalon''' (forebrain), '''mesencephalon''' (midbrain), '''rhombencephalon''' (hindbrain)


===Secondary Vesicles===
===Nervous System Regionalization Entails Axial Allocation before Neural Differentiation===
[[Image:CNS secondary vesicles.jpg]]


From the 3 primary vesicles developing to form 5 secondary vesicles
Cell. 2018 Oct 13. pii: S0092-8674(18)31252-2. doi: 10.1016/j.cell.2018.09.040. [Epub ahead of print]
* prosencephalon- '''telencephalon''' (endbrain, forms cerebral hemispheres), '''diencephalon''' (betweenbrain, forms optic outgrowth)
* '''mesencephalon'''
* rhombencephalon- '''metencephalon''' (behindbrain), '''myelencephalon''' (medullabrain)


==Ventricles==
Metzis V1, Steinhauser S1, Pakanavicius E1, Gouti M2, Stamataki D1, Ivanovitch K1, Watson T1, Rayon T1, Mousavy Gharavy SN1, Lovell-Badge R1, Luscombe NM3, Briscoe J4.
[[Image:Csf_cartoon2.jpg|thumb|CNS ventricles]]
Author information
MH - this will be covered in detail in later neural development
Abstract
Neural induction in vertebrates generates a CNS that extends the rostral-caudal length of the body. The prevailing view is that neural cells are initially induced with anterior (forebrain) identity; caudalizing signals then convert a proportion to posterior fates (spinal cord). To test this model, we used chromatin accessibility to define how cells adopt region-specific neural fates. Together with genetic and biochemical perturbations, this identified a developmental time window in which genome-wide chromatin-remodeling events preconfigure epiblast cells for neural induction. Contrary to the established model, this revealed that cells commit to a regional identity before acquiring neural identity. This "primary regionalization" allocates cells to anterior or posterior regions of the nervous system, explaining how cranial and spinal neurons are generated at appropriate axial positions. These findings prompt a revision to models of neural induction and support the proposed dual evolutionary origin of the vertebrate CNS.
KEYWORDS:
ATAC-seq; CDX; WNT signaling; chromatin; computational genomics; embryonic development; gene regulation; neural induction; spinal cord; stem cells and development
PMID: 30343898 DOI: 10.1016/j.cell.2018.09.040


* cavity within tube will form the contiguious space of the ventricules of the brain and central canal of spinal cord
* this space is filled initially with amniotic fluid, later with CerebroSpinal Fluid (CSF)
* CSF is secreted by a modified vascular structure, the '''chorioid plexus''', lying within the ventricles
** (More? [[http://embryology.med.unsw.edu.au/Notes/neuron6.htm Notes Chorioid Plexus])


===Brain Flexures===
==2017==
Rapid growth folds the neural tube forming 3 brain flexures
* '''cervical flexure''' - between brain stem and spinal cord
* '''midbrain flexure''' - pushes mesencephalon upwards
* '''pontine flexure''' - generates 4th ventricle


==Neural Layers==
===Molecular and cellular reorganization of neural circuits in the human lineage===
[[Image:Stage22 HPA1L.jpg|thumb|Stage 22 developing head cross section]]
Science. 2017 Nov 24;358(6366):1027-1032. doi: 10.1126/science.aan3456.
[[Image:Stage22 HPA2L.jpg|thumb|Stage 22 developing cortex]]
[[Image:Neuron_cartoon.jpg|thumb|Neuron and supporting glial cells]]
* neural stem cells lie in the layer closest to the ventricular space, the '''ventricular layer'''
** this layer generates both neuroblasts and glioblasts
'''Neuroblasts''' - neurons arise first as neuroblasts and migrate along radial gial, their migration stops at cortical plate.
'''Glioblasts''' - glia arise later as glioblasts


Both neurons and glia undergo a complex process of growth, differentiation and interaction over a long developmental time period.
Sousa AMM1, Zhu Y1, Raghanti MA2, Kitchen RR3,4, Onorati M1,5, Tebbenkamp ATN1, Stutz B6, Meyer KA1, Li M1, Kawasawa YI1,7, Liu F1, Perez RG8, Mele M8, Carvalho T8, Skarica M1, Gulden FO1, Pletikos M1, Shibata A1, Stephenson AR2, Edler MK2, Ely JJ9, Elsworth JD4, Horvath TL1,6, Hof PR10, Hyde TM11, Kleinman JE11, Weinberger DR11, Reimers M12, Lifton RP13,14,15, Mane SM16, Noonan JP13, State MW17, Lein ES18, Knowles JA19, Marques-Bonet T8,20,21, Sherwood CC22, Gerstein MB3, Sestan N23,4,6,13,24.


==Spinal Cord Axes==
Identified by experimental manipulation of interactions.
* Initial experiments looked at how isolated tissues may influence the development of the spinal cord.
* Repositionining of specific tissues both in vivo and in vitro
* specific markers of or alteration of differentiation. '''Notocord Induction'''


===Ventral Axis===
Abstract
[[Image:Sonic_hedgehog_expression.jpg|thumb|Notochord secreting sonic hedgehog]]
To better understand the molecular and cellular differences in brain organization between human and nonhuman primates, we performed transcriptome sequencing of 16 regions of adult human, chimpanzee, and macaque brains. Integration with human single-cell transcriptomic data revealed global, regional, and cell-type-specific species expression differences in genes representing distinct functional categories. We validated and further characterized the human specificity of genes enriched in distinct cell types through histological and functional analyses, including rare subpallial-derived interneurons expressing dopamine biosynthesis genes enriched in the human striatum and absent in the nonhuman African ape neocortex. Our integrated analysis of the generated data revealed diverse molecular and cellular features of the phylogenetic reorganization of the human brain across multiple levels, with relevance for brain function and disease.
* Sonic Hedgehog (SHH) - notochord secretes sonic hedgehog
PMID: 29170230
* Gene expression studies (ISH) showed shh gene expression occured in a subset of inducing tissues
* has a patterning role elsewhere (limb, sclerotome, lung)
* 2 signaling activities acting (locally and at a distance) Ventral- Sonic Hedgehog
* Binds to cell surface receptor patched
* without shh, patched (Ptc) binds smoothened (Smo)
* with shh shh-Ptc releases Smo activating G protein pathway '''Gene Diseases'''
* shh Human mutation- holoprosencephaly 3
** characteristic faces of the severe form of HPE which included a single fused eye (cyclopia) and a nose-like structure (proboscis) above the eye
** Downstream targets of Sonic hedgehog signalling:
*** transcription factors like Gli3 (responsible for Greigs polycephalosyndactyly in humans)
*** d Hoxd13 (responsible for polysyndactyly)


===Dorsal Axis===  
===Mouse Fgf8-Cre-LacZ lineage analysis defines the territory of the postnatal mammalian isthmus===
* Dorsalin - ectoderm secretes a growth factor shown to controls patterning in embryonic mesoderm (frog)
J Comp Neurol. 2017 Aug 15;525(12):2782-2799. doi: 10.1002/cne.24242. Epub 2017 May 30.
** Transforming Growth factor beta, (TGF b), related factors BMP-2, BMP-4, BMP-7, radar (flies related protein determines dorsoventral)
** homology search of vertebrate library identified protein of same family.  
** dorsalin-1 (dsl-1) (Basler, Cell 73, p687, 1993) Dorsalin-1
** From overlying ectoderm
** Naming comes from the obvious reason that it promotes the differentiation of neural crest cells.  
** Also signal for dorsal signal of neural tube.  
** Inhibits the differentiation of motoneurons.  
** Implication is that dsl-1 and shh act antagonistically, or competitively to establish d-v axis of neural tube.


===Rostro-Caudal Axis===
Watson C1, Shimogori T2, Puelles L3.
* Brain rostro-caudal axis is generated by differential expression of Hox genes (transcriptional activators)
** corresponding to genetic order on chromosome. (Wilkinson, Nature, 341, p405, 1989) Hox Genes
** Stands for '''H'''omeob'''ox''' domain Genes
** A family of transcription factors
** Discovered in flies and conserved between all species. [../OtherEmb/fly.htm#antennapedia antennapedia]
** Expressed in sequence along the embryo rostro-caudal axis.
** Regulate many other aspects of development.
** 180aa region binds DNA and regulate gene expression
** large family of genes organized and expressed in sequence on the chromosome
** Nkx-2.2 first detected at 1 somite stage
** Lim hox gene expressed at spinal cord level


==Ectodermal Placodes==
Abstract
* Specialized ectodermal "patches" in the head region
* Contribute sensory structures - otic placode (otocyst), nasal placode, lens placode
* Contribute teeth


== Human Neuralation - Early Stages ==
The isthmus is recognized as the most rostral segment of the hindbrain in non-mammalian vertebrates. In mammalian embryos, transient Fgf8 expression defines the developing isthmic region, lying between the midbrain and the first rhombomere, but there has been uncertainty about the existence of a distinct isthmic segment in postnatal mammals. We attempted to find if the region of early embryonic Fgf8 expression (which is considered to involve the entire extent of the prospective isthmus initially) might help to identify the boundaries of the isthmus in postnatal animals. By creating an Fgf8-Cre-LacZ lineage in mice, we were able to show that Fgf8-Cre reporter expression in postnatal mice is present in the same nuclei that characterize the isthmic region in birds. The 'signature' isthmic structures in birds include the trochlear nucleus, the dorsal raphe nucleus, the microcellular tegmental nuclei, the pedunculotegmental nucleus, the vermis of the cerebellum, rostral parts of the parabrachial complex and locus coeruleus, and the caudal parts of the substantia nigra and VTA. We found that all of these structures were labeled with the Fgf8-Cre reporter in the mouse brain, and we conclude that the isthmus is a distinct segment of the mammalian brain lying caudal to the midbrain and rostral to rhombomere 1 of the hindbrain.
The stages below refer to specific Carneigie stages of development.  
© 2017 Wiley Periodicals, Inc.


* '''stage 8 '''(about 18 postovulatory days) neural groove and folds are first seen
KEYWORDS:
* '''stage 9''' the three main divisions of the brain, which are not cerebral vesicles, can be distinguished while the neural groove is still completely open. [http://embryology.med.unsw.edu.au/wwwhuman/Stages/stage9sem.htm Stage 9 SEM]
Fgf8; Isthmus; RRID:AB_2313764; cerebellum; midbrain; rhombomere
* '''stage 10''' (two days later) neural folds begin to fuse near the junction between brain and spinal cord, when neural crest cells are arising mainly from the neural ectoderm [http://embryology.med.unsw.edu.au/wwwhuman/Stages/stage10sem.htm Stage 10 SEM]
PMID: 28510270 DOI: 10.1002/cne.24242
* '''stage 11''' (about 24 days) the rostral (or cephalic) neuropore closes within a few hours; closure is bidirectional, it takes place from the dorsal and terminal lips and may occur in several areas simultaneously. The two lips, however, behave differently. [http://embryology.med.unsw.edu.au/wwwhuman/Stages/stage11sem.htm Stage 11 SEM]
* '''stage 12''' (about 26 days) The caudal neuropore takes a day to close [http://embryology.med.unsw.edu.au/wwwhuman/Stages/stage12sem.htm Stage 12 SEM]
* the level of final closure is approximately at future somitic pair 31
* corresponds to the level of sacral vertebra 2
* '''stage 13''' (4 weeks) the neural tube is normally completely closed [http://embryology.med.unsw.edu.au/wwwhuman/Stages/stage13sem.htm Stage 13 SEM]


'''Secondary neurulation''' begins at stage 12 - is the differentiation of the caudal part of the neural tube from the caudal eminence (or end-bud) without the intermediate phase of a neural plate.
==2015==


(Stage text modified from: Neurulation in the normal human embryo. O'Rahilly R, Muller F Ciba Found Symp 1994;181:70-82)
===First trimester size charts of embryonic brain structures===


==Abnormalities==
Hum Reprod. 2014 Feb;29(2):201-7. doi: 10.1093/humrep/det406. Epub 2013 Nov 28.
See also [http://embryology.med.unsw.edu.au/Notes/neuron2.htm Neural Abnormalities]
[[Image:Abnormal81-92-neuron.png|thumb|Australian Birth Statistics]]
[[Image:Neural_tube_defect_meningomyelocele.jpg|thumb|Neural tube defect - Meningomyelocele]]
===Neural Tube Defects (NTD)===
Failure of neural tube closure either incorrectly or incomplete
* '''Dysraphism''' is the term often used to describe the defective fusion of the neural folds. The position and degree of failure of fusion will result in either embryonic death or a range of different neural defects. The way (mode) in which the human neural tube fuses has been a source of contention. In humans, fusion appears to initiate at multiple sites but the mode is different from that found in many animal species used in developmental studies.
* severity dependent upon level within the tube and degree of failure
* caudal failure - spina bifida cranial failure - anancephaly


====Maternal Diet====
Gijtenbeek M1, Bogers H, Groenenberg IA, Exalto N, Willemsen SP, Steegers EA, Eilers PH, Steegers-Theunissen RP.
Found that supplementation of maternal diet with folate reduces incidence of NTDs (More? [http://embryology.med.unsw.edu.au/Defect/page5e.htm Folic Acid and Neural Tube Defects])
* A randomised controlled trial conducted by the Medical Research Council of the United Kingdom demonstrated a 72% reduction in risk of recurrence by periconceptional (ie before and after conception) folic acid supplementation (4mg daily).
* Women who have one infant with a neural tube defect have a significantly increased risk of recurrence (40-50 per thousand compared with 2 per thousand for all births)
[[Image:USA spina bifida rates.jpg|300px|USA spina bifida rates]] [[Image:USA anencephaly rates.jpg|300px|USA anencephaly rates]]


In the U.S.A. the Food and Drug Administration in 1996 authorized that all enriched cereal grain products be fortified with folic acid, with optional fortification beginning in March 1996 and mandatory fortification in January 1998. The data in the above graphs show the subsequent changes in anencephaly and spina bifida rate over that period.
Abstract


===Holoprosencephaly===
STUDY QUESTION:
Can reliable size charts of human embryonic brain structures be created from three-dimensional ultrasound (3D-US) visualizations?
SUMMARY ANSWER:
Reliable size charts of human embryonic brain structures can be created from high-quality images.
WHAT IS KNOWN ALREADY:
Previous studies on the visualization of both the cavities and the walls of the brain compartments were performed using 2D-US, 3D-US or invasive intrauterine sonography. However, the walls of the diencephalon, mesencephalon and telencephalon have not been measured non-invasively before. Last-decade improvements in transvaginal ultrasound techniques allow a better visualization and offer the tools to measure these human embryonic brain structures with precision.
STUDY DESIGN, SIZE, DURATION:
This study is embedded in a prospective periconceptional cohort study. A total of 141 pregnancies were included before the sixth week of gestation and were monitored until delivery to assess complications and adverse outcomes.
PARTICIPANTS/MATERIALS, SETTING, METHODS:
For the analysis of embryonic growth, 596 3D-US scans encompassing the entire embryo were obtained from 106 singleton non-malformed live birth pregnancies between 7(+0) and 12(+6) weeks' gestational age (GA). Using 4D View (3D software) the measured embryonic brain structures comprised thickness of the diencephalon, mesencephalon and telencephalon, and the total diameter of the diencephalon and mesencephalon.
MAIN RESULTS AND THE ROLE OF CHANCE:
Of 596 3D scans, 161 (27%) high-quality scans of 79 pregnancies were eligible for analysis. The reliability of all embryonic brain structure measurements, based on the intra-class correlation coefficients (ICCs) (all above 0.98), was excellent. Bland-Altman plots showed moderate agreement for measurements of the telencephalon, but for all other measurements the agreement was good. Size charts were constructed according to crown-rump length (CRL).
LIMITATIONS, REASONS FOR CAUTION:
The percentage of high-quality scans suitable for analysis of these brain structures was low (27%).
WIDER IMPLICATIONS OF THE FINDINGS:
The size charts of human embryonic brain structures can be used to study normal and abnormal development of brain development in future. Also, the effects of periconceptional maternal exposures, such as folic acid supplement use and smoking, on human embryonic brain development can be a topic of future research.
STUDY FUNDING/COMPETING INTEREST(S):
This study was supported by the Department of Obstetrics and Gynaecology of the Erasmus University Medical Center. M.G. was supported by an additional grant from the Sophia Foundation for Medical Research (SSWO grant number 644). No competing interests are declared.
KEYWORDS:
embryo development; embryology; pregnancy; prenatal diagnosis; ultrasound


Holoprosencephaly (HPE) is developmental abnormality where the forebrain does not divide into the two separate hemispheres and ventricles.
PMID 24287820


===Critical Periods of Human Development===
===Cell cycle regulation of proliferation versus differentiation in the central nervous system===


Exposure to teratogens during these "critical periods" results in specific abnormalities. [http://embryology.med.unsw.edu.au/Medicine/images/hcriticaldev.gif Critical Periods]
Cell Tissue Res. 2015 Jan;359(1):187-200. doi: 10.1007/s00441-014-1895-8. Epub 2014 May 25.
* most systems are susceptible during embryonic development (first trimester)
* the earlier the exposure the more severe the effects
* each system has a different critical period
* longest critical periods
** longest developing systems (neural, genital)
** complicated developmental origins (sensory systems)


==Take the Quiz==
Hardwick LJ1, Ali FR, Azzarelli R, Philpott A.
<quiz display=simple>


{Ectoderm refers only to the neural plate region of the trilaminar embryo
Abstract
|type="()"}
- true
+ false
|| The entire layer of the trilaminar embryo is the '''ectoderm''' (meaning outer layer), the neural plate is only the central portion of this layer.


{The central nervous system forms in the sequence:
Formation of the central nervous system requires a period of extensive progenitor cell proliferation, accompanied or closely followed by differentiation; the balance between these two processes in various regions of the central nervous system gives rise to differential growth and cellular diversity. The correlation between cell cycle lengthening and differentiation has been reported across several types of cell lineage and from diverse model organisms, both in vivo and in vitro. Furthermore, different cell fates might be determined during different phases of the preceding cell cycle, indicating direct cell cycle influences on both early lineage commitment and terminal cell fate decisions. Significant advances have been made in the last decade and have revealed multi-directional interactions between the molecular machinery regulating the processes of cell proliferation and neuronal differentiation. Here, we first introduce the modes of proliferation in neural progenitor cells and summarise evidence linking cell cycle length and neuronal differentiation. Second, we describe the manner in which components of the cell cycle machinery can have additional and, sometimes, cell-cycle-independent roles in directly regulating neurogenesis. Finally, we discuss the way that differentiation factors, such as proneural bHLH proteins, can promote either progenitor maintenance or differentiation according to the cellular environment. These intricate connections contribute to precise coordination and the ultimate division versus differentiation decision.
|type="()"}
PMID 24859217
- norochord to neural plate to neural tube
- neural tube to neural plate to neural groove
+ neural plate to neural groove to neural tube
- neural plate to neural crest to neural zone
||The sequence '''neural plate to neural groove to neural tube''' represents the gradual folding of a flat surface sheet of ectodermal cells into a closed tube isolated from the embryo surface. The '''notochord''' is part of the mesoderm and regulates the initial overlying differentiation process. The '''neural crest''' are a population at the edge of the neural plate that do not get incorporated into the neural tube. I think I made up '''neural zone'''.


{The neural plate is narrower at the caudal (tail) end and therefore closes earlier than the broad cranial (head) end.
===Genes expressed in mouse cortical progenitors are enriched in Pax, Lhx, and Sox transcription factor putative binding sites===
|type="()"}
Brain Res. 2015 Dec 23. pii: S0006-8993(15)00961-0. doi: 10.1016/j.brainres.2015.12.022. [Epub ahead of print]
- true
+ false
|| The caudal or posterior neuropore closes after the cranial or anterior neuropore.


Bery A1, Mérot Y2, Rétaux S3.


{The correct sequence from cranial to caudal of the secondary brain vesicles is:
Abstract
|type="()"}
- prosencephalon, mesencephalon, metencephalon, myelencephalon, rhombencephalon
- telencephalon, diencephalon, metencephalon, mesencephalon, myelencephalon
+ telencephalon, diencephalon, mesencephalon, metencephalon, myelencephalon
- prosencephalon, diencephalon, mesencephalon, myelencephalon, metencephalon
||The '''prosencephalon''' and '''rhombencephalon''' are primary brain vesicles. The others are distractors using your lack of understanding of what the terms mean.


</quiz>
Considerable progress has been made in the understanding of molecular and cellular mechanisms controlling the development of the mammalian cortex. The proliferative and neurogenic properties of cortical progenitors located in the ventricular germinal zone start being understood. Little is known however on the cis-regulatory control that finely tunes gene expression in these progenitors. Here, we undertook an in silico-based approach to address this question, followed by some functional validation. Using the Eurexpress database, we established a list of 30 genes specifically expressed in the cortical germinal zone, we selected mouse/human conserved non-coding elements (CNEs) around these genes and we performed motif-enrichment search in these CNEs. We found an over-representation of motifs corresponding to binding sites for Pax, Sox, and Lhx transcription factors, often found as pairs and located within 100bp windows. A small subset of CNEs (n=7) was tested for enhancer activity, by ex-vivo and in utero electroporation assays. Two showed strong enhancer activity in the germinal zone progenitors. Mutagenesis experiments on a selected CNE showed the functional importance of the Pax, Sox, and Lhx TFBS for conferring enhancer activity to the CNE. Overall, from a cis-regulatory viewpoint, our data suggest an input from Pax, Sox and Lhx transcription factors to orchestrate corticogenesis. These results are discussed with regards to the known functional roles of Pax6, Sox2 and Lhx2 in cortical development. Copyright © 2015 Elsevier B.V. All rights reserved. KEYWORDS: Enhancer activity; Lhx2; Motif search; Mutagenesis; Non-coding regulatory element; in vivo electroporation


==UNSW Embryology Neural Links==
PMID 26721689
* [http://embryology.med.unsw.edu.au/Science/ANAT2341lecture05.htm Neural Lecture 5 2008]
* [http://embryology.med.unsw.edu.au/Notes/neuron.htm Neural Notes] | [http://embryology.med.unsw.edu.au/Notes/neuron3.htm Stage 13/14] | [http://embryology.med.unsw.edu.au/Notes/neuron4.htm Stage 22] | [http://embryology.med.unsw.edu.au/Notes/neuron5.htm#high%20power Stage 22 Brain] | [http://embryology.med.unsw.edu.au/Notes/neuron5a.htm Stage 22 Spinal Cord] | [http://embryology.med.unsw.edu.au/Notes/neuron6.htm Ventricular System] | [http://embryology.med.unsw.edu.au/Notes/neuron6a.htm Cerebrospinal Fluid] | [http://embryology.med.unsw.edu.au/Notes/neuron4a.htm Week 10] | [http://embryology.med.unsw.edu.au/Notes/neuron8.htm Fetal] | [http://embryology.med.unsw.edu.au/Notes/neuron7.htm Gliogenesis] | [http://embryology.med.unsw.edu.au/Notes/neuron_pain.htm Pain] | [http://embryology.med.unsw.edu.au/Notes/neuron11.htm Molecular]
* Abnormalities - [http://embryology.med.unsw.edu.au/Notes/neuron2.htm Abnormalities] | [http://embryology.med.unsw.edu.au/Defect/page5e.htm Folic Acid and Neural Tube Defects] | [http://embryology.med.unsw.edu.au/Medicine/images/hcriticaldev.gif Critical Periods]
* Postnatal - [http://embryology.med.unsw.edu.au/Child/page7.htm Postnatal Neural] | [http://embryology.med.unsw.edu.au/Child/page7a.htm Neural Assessment]
* [http://embryology.med.unsw.edu.au/Notes/ncrest.htm Neural Crest Notes] | [http://embryology.med.unsw.edu.au/Notes/ncrest2.htm Abnormalities][http://embryology.med.unsw.edu.au/Notes/ncrest3.htm Stage 13/14] | [http://embryology.med.unsw.edu.au/Notes/ncrest4.htm Stage 22] | [http://embryology.med.unsw.edu.au/Notes/ncrest5.htm Stage 22 high power] | [http://embryology.med.unsw.edu.au/Notes/ncrest6.htm Generation] | [http://embryology.med.unsw.edu.au/Notes/ncrest7.htm Migration] | [http://embryology.med.unsw.edu.au/Notes/ncrest8.htm Peripheral Ganglia] | [http://embryology.med.unsw.edu.au/Notes/ncrest9.htm GIT Enteric] | [http://embryology.med.unsw.edu.au/Notes/ncrest12.htm Heart] | [http://embryology.med.unsw.edu.au/Notes/ncrest10.htm Molecular] | [http://embryology.med.unsw.edu.au/Notes/ncrestlink.htm Web Links]
* [http://embryology.med.unsw.edu.au/wwwhuman/Stages/Stagesem.htm|Carnegie Stages - scanning electron micrographs]
* [http://embryology.med.unsw.edu.au/sysnote.htm System Notes]
* [http://embryology.med.unsw.edu.au/week/weekbyweek.htm Development Timeline]


== Internet Links ==
===Development of the vertebrate tailbud===
Wiley Interdiscip Rev Dev Biol. 2015 Jan-Feb;4(1):33-44. doi: 10.1002/wdev.163. Epub 2014 Nov 10.


* '''Embryo Images'''  [http://www.med.unc.edu/embryo_images/unit-bdyfm/bdyfm_htms/bdyfmtoc.htm Early Cell Populations and Establishment of Body Form] |  [http://www.med.unc.edu/embryo_images/unit-nervous/nerv_htms/nervtoc.htm Nervous System Development]
Beck CW1.
* '''Society for Neuroscience''' [http://web.sfn.org/content/Publications/BrainFacts/index.html http://web.sfn.org/content/Publications/BrainFacts/index.html Brain Facts]
* '''Anatomy of the Human Body''' [http://www.bartleby.com/107/7.html The Neural Groove and Tube]
* '''Environmental Health Perspectives''' [http://www.ehponline.org/members/2000/suppl-3/511-533rice/rice-full.html Critical Periods of Vulnerability for the Developing Nervous System: Evidence from Humans and Animal Models] | [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1637807 PMC: 1637807] | [http://www.ncbi.nlm.nih.gov/pubmed/10852851 PMID: 10852851]
* '''Journal''' [http://www.neuraldevelopment.com/Neural Development]


== References ==
Abstract
===Textbooks===
* '''The Developing Human: Clinically Oriented Embryology''' (8th Edition) by Keith L. Moore and T.V.N Persaud - Mesoderm Ch15,16: p405-423, 426-430 Body Cavities Ch9: p174-184
* '''Larsen’s Human Embryology''' by GC. Schoenwolf, SB. Bleyl, PR. Brauer and PH. Francis-West -  Mesoderm Ch11 p311-339 Body Cavities Ch6 p127-146


Additional Textbooks
The anatomical tailbud is a defining feature of all embryonic chordates, including vertebrates that do not end up with a morphological tail. Due to its seamless continuity with trunk tissues, the tailbud is often overlooked as a mere extension of the body axis; however, the formation of the tail from the tailbud undoubtedly involves unique and distinct mechanisms for forming axial tissues, such as the secondary neurulation process that generates the tailbud-derived spinal cord. Tailbud formation in the frog Xenopus laevis has been demonstrated to involve interaction of three posterior regions of the embryo that first come into alignment at the end of gastrulation, and molecular models for tailbud outgrowth and patterning have been proposed. While classical studies of other vertebrate models, such as the chicken, initially appeared to draw incompatible conclusions, molecular studies have subsequently shown the involvement of at least some similar genetic pathways. Finally, there is an emerging consensus that at least some vertebrate tailbud cells are multipotent progenitors with the ability to form tissues normally derived from different germ layers- a trait normally associated with regeneration of complex appendages, or stem-like cells.
* Before We Are Born (5th ed.) Moore and Persaud Ch16,17: p379-397, 399-405
© 2014 Wiley Periodicals, Inc.
* Essentials of Human Embryology Larson Ch11 p207-228
* Human Embryology Fitzgerald and Fitzgerald Body Cavities Ch5 p29-32, Ch7 p47,48
* Human Embryology and Developmental Biology ?Carlson Ch9,10: p173-193, 209-222 Body Cavities Ch5 p29-32, Ch7 p47,48


===Online Textbooks===
PMID 25382697
* '''Developmental Biology''' by Gilbert, Scott F. Sunderland (MA): Sinauer Associates, Inc.; c2000 [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?&rid=dbio.section.3455 Paraxial Mesoderm: The Somites and Their Derivatives]
* '''Molecular Biology of the Cell''' 4th ed. Alberts, Bruce; Johnson, Alexander; Lewis, Julian; Raff, Martin; Roberts, Keith; Walter, Peter New York and London: Garland Science; c2002 -  [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?&rid=mboc4.figgrp.3943 Figure 21-78. Somite formation in the chick embryo]


* '''Madame Curie Bioscience Database''' Chapters taken from the Madame Curie Bioscience Database (formerly, Eurekah Bioscience Database) Eurekah.com and Landes Bioscience and Springer Science+Business Media; c2009 [http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=eurekah&part=A16427 Patterning the Vertebrate Neural Plate by Wnt Signaling] |  [http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=eurekah&part=A55523 Neural Crest Delamination and Migration]
http://onlinelibrary.wiley.com/doi/10.1002/wdev.163/full


===Search ===
===Cellular basis of neuroepithelial bending during mouse spinal neural tube closure===


* '''Bookshelf'''  [http://www.ncbi.nlm.nih.gov/sites/entrez?db=Books&cmd=search&term=ectoderm ectoderm] | [http://www.ncbi.nlm.nih.gov/sites/entrez?db=Books&cmd=search&term=neural_plate neural plate] | [http://www.ncbi.nlm.nih.gov/sites/entrez?db=Books&cmd=search&term=neural_tube neural tube] | [http://www.ncbi.nlm.nih.gov/sites/entrez?db=Books&cmd=search&term=neural_crest neural crest]
Dev Biol. 2015 Aug 15;404(2):113-24. doi: 10.1016/j.ydbio.2015.06.003. Epub 2015 Jun 12.


* '''Pubmed''' [http://www.ncbi.nlm.nih.gov/sites/gquery?itool=toolbar&cmd=search&term=ectoderm ectoderm] | [http://www.ncbi.nlm.nih.gov/sites/gquery?itool=toolbar&cmd=search&term=neural_plate neural plate]
McShane SG1, Molè MA1, Savery D1, Greene ND1, Tam PP2, Copp AJ3.


===Reviews===
Abstract
* Temporal dynamics of patterning by morphogen gradients. Kutejova E, Briscoe J, Kicheva A. Curr Opin Genet Dev. 2009 Jul 9. [http://www.ncbi.nlm.nih.gov/pubmed/19596567 PMID: 19596567]


* The Hedgehog, TGF-beta/BMP and Wnt families of morphogens in axon guidance. Charron F, Tessier-Lavigne M. Adv Exp Med Biol. 2007;621:116-33. Review.
Bending of the neural plate at paired dorsolateral hinge points (DLHPs) is required for neural tube closure in the spinal region of the mouse embryo. As a step towards understanding the morphogenetic mechanism of DLHP development, we examined variations in neural plate cellular architecture and proliferation during closure. Neuroepithelial cells within the median hinge point (MHP) contain nuclei that are mainly basally located and undergo relatively slow proliferation, with a 7h cell cycle length. In contrast, cells in the dorsolateral neuroepithelium, including the DLHP, exhibit nuclei distributed throughout the apico-basal axis and undergo rapid proliferation, with a 4h cell cycle length. As the neural folds elevate, cell numbers increase to a greater extent in the dorsolateral neural plate that contacts the surface ectoderm, compared with the more ventromedial neural plate where cells contact paraxial mesoderm and notochord. This marked increase in dorsolateral cell number cannot be accounted for solely on the basis of enhanced cell proliferation in this region. We hypothesised that neuroepithelial cells may translocate in a ventral-to-dorsal direction as DLHP formation occurs, and this was confirmed by vital cell labelling in cultured embryos. The translocation of cells into the neural fold, together with its more rapid cell proliferation, leads to an increase in cell density dorsolaterally compared with the more ventromedial neural plate. These findings suggest a model in which DLHP formation may proceed through 'buckling' of the neuroepithelium at a dorso-ventral boundary marked by a change in cell-packing density.
[http://www.ncbi.nlm.nih.gov/pubmed/18269215 PMID: 18269215]
Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
KEYWORDS:
Cell proliferation; Embryo; Mouse; Neural tube closure; Neurulation


* Novel brain wiring functions for classical morphogens: a role as graded positional cues in axon guidance. Charron F, Tessier-Lavigne M. Development. 2005 May;132(10):2251-62. Review.
PMID 26079577
[http://www.ncbi.nlm.nih.gov/pubmed/15857918 PMID: 15857918] | [http://dev.biologists.org/cgi/content/full/132/10/2251 Development Link]


==Movies==
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4528075/


{| border='0px'
===A Functional Perspective on the Embryology and Anatomy of the Cerebral Blood Supply===


J Stroke. 2015 May;17(2):144-58. doi: 10.5853/jos.2015.17.2.144. Epub 2015 May 29.
Menshawi K1, Mohr JP1, Gutierrez J1.
Abstract
The anatomy of the arterial system supplying blood to the brain can influence the development of arterial disease such as aneurysms, dolichoectasia and atherosclerosis. As the arteries supplying blood to the brain develop during embryogenesis, variation in their anatomy may occur and this variation may influence the development of arterial disease. Angiogenesis, which occurs mainly by sprouting of parent arteries, is the first stage at which variations can occur. At day 24 of embryological life, the internal carotid artery is the first artery to form and it provides all the blood required by the primitive brain. As the occipital region, brain stem and cerebellum enlarge; the internal carotid supply becomes insufficient, triggering the development of the posterior circulation. At this stage, the posterior circulation consists of a primitive mesh of arterial networks that originate from projection of penetrators from the distal carotid artery and more proximally from carotid-vertebrobasilar anastomoses. These anastomoses regress when the basilar artery and the vertebral arteries become independent from the internal carotid artery, but their persistence is not uncommon in adults (e.g., persistent trigeminal artery). Other common remnants of embryological development include fenestration or duplication (most commonly of the basilar artery), hypoplasia (typically of the posterior communicating artery) or agenesis (typically of the anterior communicating artery). Learning more about the hemodynamic consequence that these variants may have on the brain territories they supply may help understand better the underlying physiopathology of cerebral arterial remodeling and stroke in patients with these variants. KEYWORDS: Arterial variants; Cerebral arteries; Circle of willis; Embryology; Remodeling; Stroke
PMID 26060802
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
http://synapse.koreamed.org/search.php?where=aview&id=10.5853/jos.2015.17.2.144&code=1183JOS&vmode=FT
==2014==
===A conserved role for non-neural ectoderm cells in early neural development===
Development. 2014 Nov;141(21):4127-38. doi: 10.1242/dev.107425. Epub 2014 Oct 1.
Cajal M1, Creuzet SE2, Papanayotou C1, Sabéran-Djoneidi D1, Chuva de Sousa Lopes SM3, Zwijsen A4, Collignon J1, Camus A5.
Abstract
During the early steps of head development, ectodermal patterning leads to the emergence of distinct non-neural and neural progenitor cells. The induction of the preplacodal ectoderm and the neural crest depends on well-studied signalling interactions between the non-neural ectoderm fated to become epidermis and the prospective neural plate. By contrast, the involvement of the non-neural ectoderm in the morphogenetic events leading to the development and patterning of the central nervous system has been studied less extensively. Here, we show that the removal of the rostral non-neural ectoderm abutting the prospective neural plate at late gastrulation stage leads, in mouse and chick embryos, to morphological defects in forebrain and craniofacial tissues. In particular, this ablation compromises the development of the telencephalon without affecting that of the diencephalon. Further investigations of ablated mouse embryos established that signalling centres crucial for forebrain regionalization, namely the axial mesendoderm and the anterior neural ridge, form normally. Moreover, changes in cell death or cell proliferation could not explain the specific loss of telencephalic tissue. Finally, we provide evidence that the removal of rostral tissues triggers misregulation of the BMP, WNT and FGF signalling pathways that may affect telencephalon development. This study opens new perspectives on the role of the neural/non-neural interface and reveals its functional relevance across higher vertebrates.
© 2014. Published by The Company of Biologists Ltd.
KEYWORDS:
Apoptosis; Chick; Embryo; Forebrain patterning; Mouse; Signalling centre; Telencephalon; Vertebrates
PMID 25273086
===Syndecan 4 interacts genetically with Vangl2 to regulate neural tube closure and planar cell polarity===
Development. 2013 Jul;140(14):3008-17. doi: 10.1242/dev.091173. Epub 2013 Jun 12.
Escobedo N1, Contreras O, Muñoz R, Farías M, Carrasco H, Hill C, Tran U, Pryor SE, Wessely O, Copp AJ, Larraín J.
Abstract
Syndecan 4 (Sdc4) is a cell-surface heparan sulfate proteoglycan (HSPG) that regulates gastrulation, neural tube closure and directed neural crest migration in Xenopus development. To determine whether Sdc4 participates in Wnt/PCP signaling during mouse development, we evaluated a possible interaction between a null mutation of Sdc4 and the loop-tail allele of Vangl2. Sdc4 is expressed in multiple tissues, but particularly in the non-neural ectoderm, hindgut and otic vesicles. Sdc4;Vangl2(Lp) compound mutant mice have defective spinal neural tube closure, disrupted orientation of the stereocilia bundles in the cochlea and delayed wound healing, demonstrating a strong genetic interaction. In Xenopus, co-injection of suboptimal amounts of Sdc4 and Vangl2 morpholinos resulted in a significantly greater proportion of embryos with defective neural tube closure than each individual morpholino alone. To probe the mechanism of this interaction, we overexpressed or knocked down Vangl2 function in HEK293 cells. The Sdc4 and Vangl2 proteins colocalize, and Vangl2, particularly the Vangl2(Lp) mutant form, diminishes Sdc4 protein levels. Conversely, Vangl2 knockdown enhances Sdc4 protein levels. Overall HSPG steady-state levels were regulated by Vangl2, suggesting a molecular mechanism for the genetic interaction in which Vangl2(Lp/+) enhances the Sdc4-null phenotype. This could be mediated via heparan sulfate residues, as Vangl2(Lp/+) embryos fail to initiate neural tube closure and develop craniorachischisis (usually seen only in Vangl2(Lp/Lp)) when cultured in the presence of chlorate, a sulfation inhibitor. These results demonstrate that Sdc4 can participate in the Wnt/PCP pathway, unveiling its importance during neural tube closure in mammalian embryos.
KEYWORDS:
Neural tube defects; Proteoglycans; Wnt planar cell polarity
PMID 23760952
Open Access
http://dev.biologists.org/content/140/14/3008.full?sid=38c9b5ee-04c8-4f9c-9e8f-f29d56dd1d46
===Secondary neurulation of human embryos: morphological changes and the expression of neuronal antigens===
Childs Nerv Syst. 2014 Jan;30(1):73-82. doi: 10.1007/s00381-013-2192-7. Epub 2013 Jun 13.
Yang HJ, Lee DH, Lee YJ, Chi JG, Lee JY, Phi JH, Kim SK, Cho BK, Wang KC.
Author information
Abstract
PURPOSE:
The morphological changes and expression patterns of neuronal antigens of human embryos, obtained from the therapeutic termination of pregnancy or from surgical procedures, were analyzed in order to characterize the secondary neurulation.
METHODS:
A total of 21 human embryos from Carnegie stages 12 to 23 and two fetuses in early stages were studied. The markers used for immunohistochemical study were neural cell adhesion molecule (N-CAM), neuronal nuclear antigen (NeuN), neurofilament-associated protein (3A10), synaptophysin, and glial fibrillary acidic protein (GFAP).
RESULTS:
The formation of the caudal neural tube to the tip of the caudal portion of the embryo was finished at stage 17. The postcloacal gut had completely disappeared at stage 18, and multiple cavities of the caudal neural tube were clearly visible. The caudal portion of the neural tube showed findings suggestive of involution at stage 19. The expression patterns of neuronal antigens were as follows: N-CAM and NeuN showed immunoreactivity at the germinal layer of the spinal cord at stages 17 and 18. Neurofilament-associated protein (3A10) showed persistent immunoreactivity at the caudal cell mass and notochord during the observation period, along with the spinal cord, and the positive reactions were mainly located at the dorsal white matter at stage 17. Synaptophysin showed a weak positive reaction at the caudal cell mass and notochord at stages 13 and 14, evident by staining observed at the spinal cord at stages 15 and 16. There was no definite positive reaction for GFAP.
CONCLUSIONS:
These characteristic patterns might be helpful for the understanding of human congenital anomalies involving secondary neurulation processes.
PMID 23760472
==2013==
===The longitudinal growth of the neuromeres and the resulting brain in the human embryo===
{{Ref-O'RahillyMüller2013 PMID23183269}}
Cells Tissues Organs. 2013;197(3):178-95. doi: 10.1159/000343170. Epub 2012 Nov 24.
O'Rahilly R, Müller F.
Author information
Abstract
The growth of the human brain during the embryonic period was assessed in terms of longitudinal measurements in staged embryos. Precise graphic reconstructions prepared by the onerous point-plotting method were considered to be the most reliable, and 23 were examined in detail. A distinction is necessary between measurements of the brain (cerebral diameters) and those of the skull (osseous diameters), and also between those of the folded brain in situ, studied here, and the later relatively straightened brain. Longitudinal measurements were made of individual neuromeres and their successors in steps (neuromeric lengths). The sum of the neuromeric measurements at any given stage provides the total neuromeric length (TNL) of the folded brain in situ at that stage and it increases in keeping with the greatest length (GL) of the embryo. At stages 16-19, however, the neuromeric length of the brain may exceed the GL. From stage 20 onwards the body length increases more rapidly compared with the length of the brain. The most cephalic neuromere is the telencephalon medium, abbreviated T1 here. The cerebral hemispheres are derived from it, although they are not neuromeres. The hemispheres soon extend rostrally beyond the limit of T1 by an amount that is here designated T2, and that indicates the growth of the telencephalon rostral to the commissural plate, which is the site of the future corpus callosum. Further laterally, the hemispheric length (future fronto-occipital diameter) increases rapidly, as does also the bitemporal (biparietal) diameter. At the end of the embryonic period these diameters are one fourth to one fifth of the head circumference. Additional neuromeric information becomes manifest when the measurements are calculated as percentages of the total length of the brain. The rhombencephalon decreases considerably, diencephalon 2 increases greatly, whereas diencephalon 1 diminishes, and the cerebral hemispheres enlarge massively. In addition, specific neuromeres or subdivisions come to occupy relatively more or relatively less of the total. Three periods were found during which individual neuromeres acquire their maximal or minimal lengths: the maximal absolute lengths were in period 3, whereas the maximal and minimal percentage lengths were in periods 1 and 3. The various neuromeric changes are considered to be related to alterations in functional development. Finally, in furtherance of establishing continuity in prenatal data, comparisons were effected between embryonic and fetal measurements.
Copyright © 2012 S. Karger AG, Basel.
PMID 23183269
===Neural induction and early patterning in vertebrates===
Wiley Interdiscip Rev Dev Biol. 2013 Jul;2(4):479-98. doi: 10.1002/wdev.90. Epub 2012 Oct 15.
Ozair MZ, Kintner C, Brivanlou AH.
Source
Laboratory of Molecular Vertebrate Embryology, The Rockefeller University, New York, NY, USA.
Abstract
In vertebrates, the development of the nervous system is triggered by signals from a powerful 'organizing' region of the early embryo during gastrulation. This phenomenon--neural induction--was originally discovered and given conceptual definition by experimental embryologists working with amphibian embryos. Work on the molecular circuitry underlying neural induction, also in the same model system, demonstrated that elimination of ongoing transforming growth factor-β (TGFβ) signaling in the ectoderm is the hallmark of anterior neural-fate acquisition. This observation is the basis of the 'default' model of neural induction. Endogenous neural inducers are secreted proteins that act to inhibit TGFβ ligands in the dorsal ectoderm. In the ventral ectoderm, where the signaling ligands escape the inhibitors, a non-neural fate is induced. Inhibition of the TGFβ pathway has now been demonstrated to be sufficient to directly induce neural fate in mammalian embryos as well as pluripotent mouse and human embryonic stem cells. Hence the molecular process that delineates neural from non-neural ectoderm is conserved across a broad range of organisms in the evolutionary tree. The availability of embryonic stem cells from mouse, primates, and humans will facilitate further understanding of the role of signaling pathways and their downstream mediators in neural induction in vertebrate embryos.
Copyright © 2012 Wiley Periodicals, Inc.
PMID 24014419
===Developmental mechanisms directing early anterior forebrain specification in vertebrates===
Cell Mol Life Sci. 2013 Oct;70(20):3739-52. doi: 10.1007/s00018-013-1269-5. Epub 2013 Feb 9.
Andoniadou CL, Martinez-Barbera JP.
Source
Birth Defects Research Centre, UCL Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, UK.
Abstract
Research from the last 15 years has provided a working model for how the anterior forebrain is induced and specified during the early stages of embryogenesis. This model relies on three basic processes: (1) induction of the neural plate from naive ectoderm requires the inhibition of BMP/TGFβ signaling; (2) induced neural tissue initially acquires an anterior identity (i.e., anterior forebrain); (3) maintenance and expansion of the anterior forebrain depends on the antagonism of posteriorizing signals that would otherwise transform this tissue into posterior neural fates. In this review, we present a historical perspective examining some of the significant experiments that have helped to delineate this molecular model. In addition, we discuss the function of the relevant tissues that act prior to and during gastrulation to ensure proper anterior forebrain formation. Finally, we elaborate data, mainly obtained from the analyses of mouse mutants, supporting a role for transcriptional repressors in the regulation of cell competence within the anterior forebrain. The aim of this review is to provide the reader with a general overview of the signals as well as the signaling centers that control the development of the anterior neural plate.
PMID 23397132
===Cell cycle and lineage progression of neural progenitors in the ventricular-subventricular zones of adult mice===
Proc Natl Acad Sci U S A. 2013 Mar 12;110(11):E1045-54. doi: 10.1073/pnas.1219563110. Epub 2013 Feb 21.
Ponti G, Obernier K, Guinto C, Jose L, Bonfanti L, Alvarez-Buylla A.
Source
Department of Neurological Surgery and The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA 94143, USA.
Abstract
Proliferating neural stem cells and intermediate progenitors persist in the ventricular-subventricular zone (V-SVZ) of the adult mammalian brain. This extensive germinal layer in the walls of the lateral ventricles is the site of birth of different types of interneurons destined for the olfactory bulb. The cell cycle dynamics of stem cells (B1 cells), intermediate progenitors (C cells), and neuroblasts (A cells) in the V-SVZ and the number of times these cells divide remain unknown. Using whole mounts of the walls of the lateral ventricles of adult mice and three cell cycle analysis methods using thymidine analogs, we determined the proliferation dynamics of B1, C, and A cells in vivo. Achaete-scute complex homolog (Ascl)1(+) C cells were heterogeneous with a cell cycle length (T(C)) of 18-25 h and a long S phase length (T(S)) of 14-17 h. After C cells, Doublecortin(+) A cells were the second-most common dividing cell type in the V-SVZ and had a T(C) of 18 h and T(S) of 9 h. Human glial fibrillary acidic protein (hGFAP)::GFP(+) B1 cells had a surprisingly short Tc of 17-18 h and a T(S) of 4 h. Progenitor population analysis suggests that following the initial division of B1 cells, C cells divide three times and A cells once, possibly twice. These data provide essential information on the dynamics of adult progenitor cell proliferation in the V-SVZ and how large numbers of new neurons continue to be produced in the adult mammalian brain.
PMID 23431204
==2012==
==2011==
Proc Natl Acad Sci U S A. 2011 Aug 16;108(33):13776-81. Epub 2011 Jul 27.
===Spatial and temporal second messenger codes for growth cone turning===
Nicol X, Hong KP, Spitzer NC.
Source
Neurobiology Section, Division of Biological Sciences, Kavli Institute for Brain and Mind, University of California at San Diego, La Jolla, CA 92093, USA. xavier.nicol@inserm.fr
Abstract
Cyclic AMP (cAMP) and calcium are ubiquitous, interdependent second messengers that regulate a wide range of cellular processes. During development of neuronal networks they are critical for the first step of circuit formation, transducing signals required for axon pathfinding. Surprisingly, the spatial and temporal cAMP and calcium codes used by axon guidance molecules are unknown. Here, we identify characteristics of cAMP and calcium transients generated in growth cones during Netrin-1-dependent axon guidance. In filopodia, Netrin-1-dependent Deleted in Colorectal Cancer (DCC) receptor activation induces a transient increase in cAMP that causes a brief increase in calcium transient frequency. In contrast, activation of DCC in growth cone centers leads to a transient calcium-dependent cAMP increase and a sustained increase in frequency of calcium transients. We show that filopodial cAMP transients regulate spinal axon guidance in vitro and commissural axon pathfinding in vivo. These growth cone codes provide a basis for selective activation of specific downstream effectors.
PMID 21795610
===The Zagreb Collection of human brains: a unique, versatile, but underexploited resource for the neuroscience community===
Ann N Y Acad Sci. 2011 May;1225 Suppl 1:E105-30. doi: 10.1111/j.1749-6632.2011.05993.x.
Judaš M, Šimić G, Petanjek Z, Jovanov-Milošević N, Pletikos M, Vasung L, Vukšić M, Kostović I.
Source
University of Zagreb School of Medicine, Croatian Institute for Brain Research, Zagreb, Croatia.
Abstract
The Zagreb Collection of developing and adult human brains was founded in 1974 by Ivica Kostović and consists of 1,278 developing and adult human brains, including 610 fetal, 317 children, and 359 adult brains. It is one of the largest collections of developing human brains. The collection serves as a key resource for many focused research projects and has led to several seminal contributions on mammalian cortical development, such as the discovery of the transient fetal subplate zone and of early bilaminar synaptogenesis in the embryonic and fetal human cerebral cortex, and the first description of growing afferent pathways in the human fetal telencephalon. The Zagreb Collection also serves as a core resource for ever-growing networks of international collaboration and represents the starting point for many young investigators who now pursue independent research careers at leading international institutions. The Zagreb Collection, however, remains underexploited owing to a lack of adequate funding in Croatia. Funding could establish an online catalog of the collection and modern virtual microscopy scanning methods to make the collection internationally more accessible.
© 2011 New York Academy of Sciences.
PMID: 21599691
http://www.ncbi.nlm.nih.gov/pubmed/21599691
===Plxdc2 is a mitogen for neural progenitors===
PLoS One. 2011 Jan 21;6(1):e14565.
Miller-Delaney SF, Lieberam I, Murphy P, Mitchell KJ.
Smurfit Institute of Genetics and Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
Abstract
The development of different brain regions involves the coordinated control of proliferation and cell fate specification along and across the neuraxis. Here, we identify Plxdc2 as a novel regulator of these processes, using in ovo electroporation and in vitro cultures of mammalian cells. Plxdc2 is a type I transmembrane protein with some homology to nidogen and to plexins. It is expressed in a highly discrete and dynamic pattern in the developing nervous system, with prominent expression in various patterning centres. In the chick neural tube, where Plxdc2 expression parallels that seen in the mouse, misexpression of Plxdc2 increases proliferation and alters patterns of neurogenesis, resulting in neural tube thickening at early stages. Expression of the Plxdc2 extracellular domain alone, which can be cleaved and shed in vivo, is sufficient for this activity, demonstrating a cell non-autonomous function. Induction of proliferation is also observed in cultured embryonic neuroepithelial cells (ENCs) derived from E9.5 mouse neural tube, which express a Plxdc2-binding activity. These experiments uncover a direct molecular activity of Plxdc2 in the control of proliferation, of relevance in understanding the role of this protein in various cancers, where its expression has been shown to be altered. They also implicate Plxdc2 as a novel component of the network of signalling molecules known to coordinate proliferation and differentiation in the developing nervous system.
PMID: 21283688
http://www.ncbi.nlm.nih.gov/pubmed/21283688
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3024984
'''Plxdc2''' transmembrane protein Plexin domain-containing 2. mouse Plxdc2 gene encodes a type I transmembrane protein of 530 amino acids, characterised by an extracellular region of weak nidogen homology and a plexin repeat or PSI domain, a domain found in several known axon guidance molecules.
'''Plxdc1''' In the human, mouse and chick Plxdc2 has this one related gene.
'''Molecular Patterning''' "The midbrain-hindbrain boundary (MHB), which expresses Wnt1 and Fgf8, is one of several local signalling centres in the neuroepithelium which refines AP specification of the brain. DV patterning is influenced by the floor plate, which expresses ventralising factors including sonic hedgehog (Shh) and nodal and the roof plate at the dorsal midline, which expresses members of the BMP and Wnt families. Differential dorsal and ventral growth of the brain is also co-ordinated via a signalling cascade of Shh, FGF and Wnt activity."
==2010==
===Developmental changes in cerebral grey and white matter volume from infancy to adulthood.===
Int J Dev Neurosci. 2010 Oct;28(6):481-9. Epub 2010 Jun 30.
Groeschel S, Vollmer B, King MD, Connelly A.
Radiology and Physics Unit, UCL Institute of Child Health, London, UK. s.groeschel@gmx.org
Abstract
In order to quantify human brain development in vivo, high resolution magnetic resonance images of 158 normal subjects from infancy to young adulthood were studied (age range 3 months-30 years, 71 males, 87 females). Data were analysed using algorithms based on voxel-based morphometry (VBM) (an objective whole brain processing technique) to generate global volume measures of whole brain, grey matter (GM) and white matter (GM). Gender-specific development of WM and GM volumes is characterised using a piecewise polynomial growth curve model to account for the non-linear nature of human brain development, implemented using Markov chain Monte Carlo simulation. The statistical method employed in this study proved to be successful and robust in the characterisation of brain development. The resulting growth curve parameter estimates lead to the following observations: total brain volume is demonstrated to undergo an initial rapid spurt. The total GM volume peaks during childhood and decreases thereafter, whereas total WM volume increases up to young adulthood. Relative to brain size, GM decreases and WM increases markedly over this age range in a non-linear manner, resulting in an increasing WM-to-GM ratio over much of the observed age range. In addition, significant gender differences are found. In general, brain volume and total white and grey matter volume are larger in males than in females, with a time-dependent difference over the age range studied. Over part of the observed age range females tend to have more GM volume relative to brain size and lower WM-to-GM ratio than males. The presented findings should be taken into account when investigating physiological and pathological changes during brain development.
http://www.ncbi.nlm.nih.gov/pubmed/20600789
==2009==
===Heterogeneity in subcortical brain development: A structural magnetic resonance imaging study of brain maturation from 8 to 30 years.===
J Neurosci. 2009 Sep 23;29(38):11772-82.
Ostby Y, Tamnes CK, Fjell AM, Westlye LT, Due-Tønnessen P, Walhovd KB.
Center for the Study of Human Cognition, Department of Psychology, University of Oslo, Norway. ylva.ostby@psykologi.uio.no
Abstract
Brain development during late childhood and adolescence is characterized by decreases in gray matter (GM) and increases in white matter (WM) and ventricular volume. The dynamic nature of development across different structures is, however, not well understood, and the present magnetic resonance imaging study took advantage of a whole-brain segmentation approach to describe the developmental trajectories of 16 neuroanatomical volumes in the same sample of children, adolescents, and young adults (n = 171; range, 8-30 years). The cerebral cortex, cerebral WM, caudate, putamen, pallidum, accumbens area, hippocampus, amygdala, thalamus, brainstem, cerebellar GM, cerebellar WM, lateral ventricles, inferior lateral ventricles, third ventricle, and fourth ventricle were studied. The cerebral cortex was further analyzed in terms of lobar thickness and surface area. The results revealed substantial heterogeneity in developmental trajectories. GM decreased nonlinearly in the cerebral cortex and linearly in the caudate, putamen, pallidum, accumbens, and cerebellar GM, whereas the amygdala and hippocampus showed slight, nonlinear increases in GM volume. WM increased nonlinearly in both the cerebrum and cerebellum, with an earlier maturation in cerebellar WM. In addition to similarities in developmental trajectories within subcortical regions, our results also point to differences between structures within the same regions: among the basal ganglia, the caudate showed a weaker relationship with age than the putamen and pallidum, and in the cerebellum, differences were found between GM and WM development. These results emphasize the importance of studying a wide range of structural variables in the same sample, for a broader understanding of brain developmental principles.
http://www.ncbi.nlm.nih.gov/pubmed/19776264 http://www.jneurosci.org/cgi/content/full/29/38/11772
==2008==
===Progressive loss of PAX6, TBR2, NEUROD and TBR1 mRNA gradients correlates with translocation of EMX2 to the cortical plate during human cortical development===
Eur J Neurosci. 2008 Oct;28(8):1449-56.
Bayatti N, Sarma S, Shaw C, Eyre JA, Vouyiouklis DA, Lindsay S, Clowry GJ.
Source
Institute of Neuroscience, Newcastle University, Newcastle-upon-Tyne, UK.
Abstract
The transcription factors Emx2 and Pax6 are expressed in the proliferating zones of the developing rodent neocortex, and gradients of expression interact in specifying caudal and rostral identities. Pax6 is also involved in corticoneurogenesis, being expressed by radial glial progenitors that give rise to cells that also sequentially express Tbr2, NeuroD and Tbr1, genes temporally downstream of Pax6. In this study, using in situ hybridization, we analysed the expression of EMX2, PAX6, TBR2, NEUROD and TBR1 mRNA in the developing human cortex between 8 and 12 postconceptional weeks (PCW). EMX2 mRNA was expressed in the ventricular (VZ) and subventricular zones (SVZ), but also in the cortical plate, unlike in the rodent. However, gradients of expression were similar to that of the rodent at all ages studied. PAX6 mRNA expression was limited to the VZ and SVZ. At 8 PCW, PAX6 was highly expressed rostrally but less so caudally, as has been seen in the rodent, however this gradient disappeared early in corticogenesis, by 9 PCW. There was less restricted compartment-specific expression of TBR2, NEUROD and TBR1 mRNA than in the rodent, where the gradients of expression were similar to that of PAX6 prior to 9 PCW. The gradient disappeared for TBR2 by 10 PCW, and for NEUROD and TBR1 by 12 PCW. These data support recent reports that EMX2 but not PAX6 is more directly involved in arealization, highlighting that analysis of human development allows better spatio-temporal resolution than studies in rodents.
PMID 18973570
===A structural MRI study of human brain development from birth to 2 years.===
Knickmeyer RC, Gouttard S, Kang C, Evans D, Wilber K, Smith JK, Hamer RM, Lin W, Gerig G, Gilmore JH.
J Neurosci. 2008 Nov 19;28(47):12176-82.
PMID 19020011
==2004==
===3 dimensional modelling of early human brain development using optical projection tomography===
BMC Neurosci. 2004 Aug 6;5:27.
Kerwin J, Scott M, Sharpe J, Puelles L, Robson SC, Martínez-de-la-Torre M, Ferran JL, Feng G, Baldock R, Strachan T, Davidson D, Lindsay S.
Source
Institute of Human Genetics, University of Newcastle upon Tyne, International Centre for Life, Central Parkway, Newcastle upon Tyne, NE1 3BZ, UK. j.m.kerwin@ncl.ac.uk
Abstract
BACKGROUND:
As development proceeds the human embryo attains an ever more complex three dimensional (3D) structure. Analyzing the gene expression patterns that underlie these changes and interpreting their significance depends on identifying the anatomical structures to which they map and following these patterns in developing 3D structures over time. The difficulty of this task greatly increases as more gene expression patterns are added, particularly in organs with complex 3D structures such as the brain. Optical Projection Tomography (OPT) is a new technology which has been developed for rapidly generating digital 3D models of intact specimens. We have assessed the resolution of unstained neuronal structures within a Carnegie Stage (CS)17 OPT model and tested its use as a framework onto which anatomical structures can be defined and gene expression data mapped.
RESULTS:
Resolution of the OPT models was assessed by comparison of digital sections with physical sections stained, either with haematoxylin and eosin (H&E) or by immunocytochemistry for GAP43 or PAX6, to identify specific anatomical features. Despite the 3D models being of unstained tissue, peripheral nervous system structures from the trigeminal ganglion (approximately 300 microm by approximately 150 microm) to the rootlets of cranial nerve XII (approximately 20 microm in diameter) were clearly identifiable, as were structures in the developing neural tube such as the zona limitans intrathalamica (core is approximately 30 microm thick). Fourteen anatomical domains have been identified and visualised within the CS17 model. Two 3D gene expression domains, known to be defined by Pax6 expression in the mouse, were clearly visible when PAX6 data from 2D sections were mapped to the CS17 model. The feasibility of applying the OPT technology to all stages from CS12 to CS23, which encompasses the major period of organogenesis for the human developing central nervous system, was successfully demonstrated.
CONCLUSION:
In the CS17 model considerable detail is visible within the developing nervous system at a minimum resolution of approximately 20 microm and 3D anatomical and gene expression domains can be defined and visualised successfully. The OPT models and accompanying technologies for manipulating them provide a powerful approach to visualising and analysing gene expression and morphology during early human brain development.
PMID 15298700
==1997==
===The timing and sequence of appearance of neuromeres and their derivatives in staged human embryos===
Acta Anat (Basel). 1997;158(2):83-99.
Müller F, O'Rahilly R.
Author information
Abstract
Serial sections of 215 human embryos from Carnegie stages 6-17 were investigated, and 85 graphic reconstructions were prepared. It is proposed that neuromeres be defined as morphologically identifiable transverse subdivisions perpendicular to the longitudinal axis of the embryonic brain and extending onto both sides of the body. It is proposed further that primary neuromeres be redefined as the early-appearing larger divisions of the open neural folds, and secondary neuromeres as the smaller subdivisions that are found both before and after closure of the neural tube. In the light of these definitions, 6 primary neuromeres can be detected in the human brain at stage 9, and a maximum of 16 secondary neuromeres at stage 14. The relationships of the 8 rhombomeres to the associated neural crest, as well as to the pharyngeal arches and the exits of the cranial nerves, are tabulated. Rhombomere 8 (Rh. 8) is intermediate between the more rostral neuromeres and the spinal cord, and its neural relationships indicate that the four occipital somitic pairs do not impress a strictly repetitive pattern as in the spinal cord. Hence, it is suggested that Rh. 8 depends on both intrinsic and extrinsic factors. The synencephalon, parencephalon, and isthmic neuromere can be distinguished in stage 13. In stage 14, rostral and caudal portions of the parencephalon are recognizable, and the full complement of 16 neuromeres is now present. The medial ventricular eminence appears in the diencephalon (D1). A longitudinal organisation begins to be superimposed on the neuromeres, as now indicated by the appearance of the hypothalamic cell cord. This continues in stage 15, when the hypothalamic sulcus develops. That groove, however, is not continuous with the sulcus limitans. In the diencephalon, five longitudinal zones can be discerned. In stage 16, fibre tracts, such as the habenulo-interpeduncular (fasciculus retroflexus) and the tract of the posterior commissure, outline the boundaries of the synencephalon. In stage 17, the tract of the zona limitans intrathalamica (along the marginal ridge in the parencephalon) is an important landmark. This is the last stage in which all the neuromeres can be distinguished. The supramamillary recess becomes defined and is the termination of the sulcus limitans: the alar/basal distinction is inappropriate in the human forebrain. The number and identity of the neuromeres in the human brain, their precise sequence of appearance, and the stages at which they appear are here clarified for the first time. The results of various studies of domains of gene expression indicate that, although in some instances such territories follow the morphological neuromeres, in others they may cross interneuromeric boundaries. It is concluded that the precise morphological study of neuromeres in any given species is necessary for correlative investigations of gene expression.
PMID 9311417
==1994==
===Neurulation in the normal human embryo===
Ciba Found Symp. 1994;181:70-82; discussion 82-9.
O'Rahilly R, Müller F.
Source
Institut für Anatomie und Spezielle Embryologie, Universität Freiburg, Switzerland.
Abstract
The neural groove and folds are first seen during stage 8 (about 18 postovulatory days). Two days later (stage 9) the three main divisions of the brain, which are not cerebral vesicles, can be distinguished while the neural groove is still completely open. Two days later (stage 10) the neural folds begin to fuse near the junction between brain and spinal cord, when neural crest cells are arising mainly from the neural ectoderm. The rostral (or cephalic) neuropore closes within a few hours during stage 11 (about 24 days). The closure is bidirectional; it takes place from the dorsal and terminal lips and may occur in several areas simultaneously. The two lips, however, behave differently. The caudal neuropore takes a day to close during stage 12 (about 26 days) and the level of final closure is approximately at future somitic pair 31, which corresponds to the level of sacral vertebra 2. At stage 13 (4 weeks) the neural tube is normally completely closed. Secondary neurulation, which begins at stage 12, is the differentiation of the caudal part of the neural tube from the caudal eminence (or end-bud) without the intermediate phase of a neural plate.
PMID 8005032
==Neural Development Table==
{| style="width:90%" border=1 cellpadding=3 cellspacing=0
|-bgcolor="CEDFF2" 
|  valign=top| '''Neural Tube'''
|  valign=top| '''Primary Vesicles'''
|  valign=top| '''Secondary Vesicles'''
|  valign=top| '''Adult Structures'''
|-
|-
| [[File:Neuralplate_001 icon.jpg|90px|link=Development Animation - Neural Plate]]
|   rowspan=5 valign=middle| Brain
| [[File:Neuraltube_001 icon.jpg|90px|link=Development Animation - Neural Tube]]
|  rowspan=2 valign=middle| Prosencephalon
|  
|  valign=top| Telencephalon
|-
| valign=top| Rhinencephalon, Amygdala, Hippocampus, Neocortex, Basal Ganglia, Lateral Ventricles
| [[Development Animation - Neural Plate|Neural Plate]]
|-  
| [[Development Animation - Neural Tube|Neural Tube]]
|   valign=top| Diencephalon
|  
| valign=top| Epithalamus, Thalamus, Hypothalamus, Subthalamus, Pituitary, Pineal, Third ventricle
|-  
|   valign=top| Mesencephalon
|  valign=top| Mesencephalon
|  valign=top| Tectum, Cerebral peduncle, Pretectum, Cerebral aqueduct
|-  
|   rowspan=2 valign=middle| Rhombencephalon
|  valign=top| Metencephalon
|  valign=top| Pons, Cerebellum
|-  
|  valign=top| Myelencephalon
|  valign=top| Medulla oblongata
|-
|  colspan=4 valign=top | Spinal Cord
|}
 
==Neural Table Linked==
 
 
{| style="width:90%" border=1 cellpadding=3 cellspacing=0
|-bgcolor="CEDFF2" 
|  valign=top| '''Neural Tube'''
|  valign=top| '''Primary Vesicles'''
|  valign=top| '''Secondary Vesicles'''
| valign=top| '''Adult Structures'''
|-
|-
|  rowspan=5 valign=middle| Brain
|  rowspan=2 valign=middle| [[Neural_-_Prosencephalon_Development|Prosencephalon]]
|  valign=top| [[Neural_-_Telencephalon_Development|Telencephalon]]
|  valign=top| Rhinencephalon, [[Neural_-_Amygdala_Development|Amygdala]],  [[Neural_-_Hippocampus_Development|Hippocampus]], Neocortex, [[Neural_-_Basal_Ganglia_Development|Basal Ganglia]], [[Neural_-_Ventricular_System_Development|lateral ventricles]]
|-
|  valign=top| [[Neural_-_Diencephalon_Development|Diencephalon]]
|  valign=top| [[Neural_-_Epithalamus_Development|Epithalamus]],  [[Neural_-_Thalamus_Development|Thalamus]], [[Endocrine_-_Hypothalamus_Development|Hypothalamus]], Subthalamus, [[Endocrine_-_Pituitary_Development|Pituitary]], [[Endocrine_-_Pineal_Development|Pineal]], [[Neural_-_Ventricular_System_Development|third ventricle]]
|-
|  valign=top| [[Neural_-_Mesencephalon_Development|Mesencephalon]]
|  valign=top| [[Neural_-_Mesencephalon_Development|Mesencephalon]]
|  valign=top| [[Neural_-_Tectum_Development|Tectum]], Cerebral peduncle, Pretectum, [[Neural_-_Ventricular_System_Development|cerebral aqueduct]]
|-
|    rowspan=2 valign=middle| [[Neural_-_Rhombencephalon_Development|Rhombencephalon]]
|  valign=top| [[Neural_-_Metencephalon_Development|Metencephalon]]
|  valign=top| Pons, [[Neural_-_Cerebellum_Development|Cerebellum]]
|-
|  valign=top| [[Neural_-_Myelencephalon_Development|Myelencephalon]]
|  valign=top| [[Neural_-_Medulla_Oblongata_Development|Medulla Oblongata]]
|-
|  colspan=4 valign=top | [[Neural_-_Spinal_Cord_Development|Spinal Cord]]
|}
|}


== Neural Development Terms ==
{{Template:Neural Links 2}}
Only brief descriptions are given below, more complete definitions can be found in the [[glossary]].
 
* '''3DMRI''' Three-dimensional magnetic resonance imaging. A new technique that allows 3D analysis of embryonic structures. (More? [http://embryology.med.unsw.edu.au/Defect/MRI.htm Prenatal Diagnosis - Magnetic Resonance Imaging])
* '''3rd ventricle''' a fluid-filled space formed from neural tube lumen, located within the diencephalon (from the primary vesicle prosencephalon, forebrain).
* '''4th ventricle''' a fluid-filled space formed from neural tube lumen, located within the rhombencephalon (from the primary vesicle, hindbrain).
* '''adenohypophysis''' (anterior pituitary) = 3 parts pars distalis, pars intermedia, pars tuberalis.
* '''alar plate''' afferent, dorsal horns
* '''anlage''' (German = primordium, structure or cells which will form a future structure.
* '''arachnoid''' - (G.) spider web-like
* '''basal ganglia''' -  (basal nuclei) neural structure derived from the secondary vesicle telencephalon (endbrain) structure from the earlier primary vesicle prosencephalon (forebrain)
* '''basal plate''' efferent, ventral horns
* '''brachial plexus''' mixed spinal nerves innervating the upper limb form a complex meshwork (crossing).
* '''brain''' general term for the central nervous system formed from 3 primary vesicles.
* '''buccopharyngeal membrane''' (=oral membrane) at cranial (mouth) end of gastrointestinal tract (GIT) where surface ectoderm and GIT endoderm meet. (see also [#cloacal membrane cloacal membrane])
* '''cauda equina''' - (=horse's tail) caudal extension of the mature spinal cord.
* '''central canal''' lumen, cavity of neural tube within the spinal cord. Space is continuous with ventricular system of the brain.
* '''cerebral aqueduct''' ventricular cavity within the mesencephalon.
* '''cervical flexure''' most caudal brain flexure (of 3) between spinal cord and rhompencephalon. ( sc-'''^'''V^ )
* '''choroid plexus''' specialized vascular plexus responsible for secreting ventricular fluid that with further additions becomes cerebrospinal fluid (CSF).
* '''cloacal membrane''' at caudal (anal) end of gastrointestinal tract (GIT) where surface ectoderm and GIT endoderm meet forms the openings for GIT, urinary, reproductive tracts. (see also buccopharyngeal membrane)
* '''cortex''' - CNS structure derived from the secondary vesicle telencephalon (endbrain) from the earlier primary vesicle prosencephalon (forebrain).
* '''cortical plate''' outer neural tube region which post-mitotic neuroblasts migrate too along radial glia to form adult cortical layers.
* '''cranial flexure''' (=midbrain flexure) most cranial brain flexure (of 3) between mesencephalon and prosencephalon. ( sc-^V'''^''' )
* '''diencephalon''' the caudal portion of forebrain after it divides into 2 parts in the 5 secondary vesicle brain (week 5). (cavity- 3rd ventricle) Forms the thalmus and other nuclei in the adult brain. (sc-My-Met-Mes-'''Di'''-Tel)
* '''dorsal root ganglia''' (=spinal ganglia) sensory ganglia derived from the neural crest lying laterally paired and dorsally to the spinal cord (in the embryo found ventral to the spinal cord). Connects centrally with the dorsal horn of the spinal cord.
* '''dura mater'''- "tough" (Latin, ''mater'' = mother)
* '''ectoderm''' the germ layer which form the nervous system from the neural tube and neural crest.
* '''ependyma''' epithelia of remnant cells after neurons and glia have been generated and left the ventricular zone
* '''floorplate''' early forming thin region of neural tube closest to the notochord.
* '''ganglia''' (pl. of ganglion) specialized neural cluster.
* '''glia''' supporting, non-neuronal cells of the nervous system. Generated from neuroepithelial stem cells in ventricular zone of neural tube. Form astrocytes, oligodendrocytes.
* '''grey matter''' neural regions containing cell bodies (somas) of neurons. In the brain it is the outer layer, in the spinal cord it is inner layer. (see white matter white matter)
* '''growth factor''' usually a protein or peptide that will bind a cell membrane receptor and then activates an intracellular signaling pathway. The function of the pathway will be to alter the cell directly or indirectly by changing gene expression. (eg shh)
* '''hox''' (='''h'''omeob'''ox''') family of transcription factors that bind DNA and activate gene expression. Expression of different Hox genes along neural tube defines rostral-caudal axis and segmental levels.
* '''hydrocephalus''' abnormality as the result of an imbalance between the rate at which the CSF is being formed and the rate at which the CSF is passing through the arachnoidal villi back into the blood (hydrocephalus rate is a function of the degree of imbalance in these two). Very small imbalance exhibit subtle, if any, symptoms. Large imbalances will have rapidly evolving symptoms of unmistakable import.
* '''isthmus'''- (G. narrow passage)
* '''lamina terminalis''' anterior region of brain where cranial neuropore closes.
* '''lumbar plexus''' mixed spinal nerves innervating the lower limb form a complex meshwork (crossing).
* '''mantle layer''' layer of cells generated by first neuroblasts migrating from the ventricular zone of the neural tube. Layers are rearranged during development of the brain and spinal cord. (Ven-'''Man'''-Mar-CP)
* '''marginal zone''' layer of processes from neuroblasts in mantle layer. (Ven-Man-'''Mar'''-CP)
* '''mater''' (Latin, ''mater'' = mother)
* '''meninges''' mesenchyme surrounding neural tube forms 3 layer (Dura-, pia-, arachnoid- mater) connective tissue sheath of nervous system. (D-P-A-cns)
* '''mesencephalon''' (=midbrain), the middle portion of the 3 primary vesicle brain (week 4). (sc-R-'''M'''-P)
* '''metencephalon''' the cranial portion of hindbrain after it divides into 2 parts in the 5 secondary vesicle brain (week 5). Forms the pons and cerebellum in the adult brain. (sc-My-'''Met'''-Mes-Di-Tel)
* '''myelencephalon''' the caudal portion of hindbrain after it divides into 2 parts in the 5 secondary vesicle brain (week 5). Forms the medulla in the adult brain. (sc-'''My'''-Met-Mes-Di-Tel)
* '''neural tube''' neural plate region of ectoderm pinched off to form hollow ectodermal tube above notochord in mesoderm.
* '''neural tube defect''' (NTD) any developmental abnormality that affects neural tube development. Commonly failure of neural tube closure.
* '''neuroblast''' undifferentiated neuron found in ventricular layer of neural tube.
* '''neurohypophysis''' (=posterior pituitary=pas nervosa)
* '''neuron''' The cellur "unit" of the nervous system, transmitting signals between neurons and other cells. The post-mitotic cells generated from neuroepithelial stem cells (neuroblasts) in ventricular zone of neural tube.
* '''neuropore''' opening at either end of neural tube: cranial=rostral=anterior, caudal=posterior. The cranial neuropore closes (day 25) approx. 2 days (human) before caudal.
* '''notochord''' rod of cells lying in mesoderm layer ventral to the neural tube, induces neural tube and secretes sonic hedgehog which "ventralizes" the neural tube.
* '''olfactory bulb''' (=cranial nerve I, CN I) bipolar neurons from nasal epithelium project axons through cribiform palate into olfactory bulb of the brain.
* optic cup-
* '''optic nerve''' (=cranial nerve II, CN II) retinal ganglion neurons project from the retina as a tract into the brain (at the level of the diencephalon).
* '''otocyst''' (=otic vesicle) sensory [#placode placode] which sinks into mesoderm to form spherical vesicle (stage 13/14 embryo) that will form components of the inner ear.
* '''pars''' (L. part of)
* '''pharyngeal arches''' (=branchial arches, Gk. gill) form structures of the head. Six arches form but only 4 form any structures. Each arch has a pouch, membrane and cleft.
* '''pharynx''' uppermost end of GIT, beginning at the buccopharyngeal membrane and at the level of the pharyngeal arches.
* pia mater-
* '''placode''' specialized regions of ectoderm which form components of the sensory apparatus.
* '''pontine flexure''' middle brain flexure (of 3) between cervical and cranial flexure in opposite direction, also generates thin roof of rhombencephalon and divides it into myelencephalon and metencephalon. ( sc-^'''V'''^ )
* '''prosencephalon''' (=forebrain), the most cranial portion of the 3 primary vesicle brain (week 4).  (sc-R-M-'''P''')
* '''Rathke's pouch''' a portion of the roof of the pharynx pushes upward towards the floor of the brain forming the anterior pituirary (adenohypophysis, pars distalis, pars tuberalis pars intermedia). Where it meets a portion of the brain pushing downward forming the posterior pituitary (neurohypophysis, pars nervosa). Rathke's pouch eventually looses its connection with the pharynx. (Martin Heinrich Rathke 1973-1860, embryologist and anatomist)
* '''rhombencephalon''' (=hindbrain), the most caudal portion of the 3 primary vesicle brain (week 4). (sc-'''R'''-M-P)
* '''roofplate''' early forming thin region of neural tube closest to the overlying ectoderm.
* '''spinal cord''' caudal end of neural tube that does not contribute to brain. Note: the process of secondary neuralation contributes the caudal end of the spinal cord.
* '''spinal ganglia''' (=dorsal root ganglia, drg) sensory ganglia derived from the neural crest lying laterally paired and dorsally to the spinal cord (in the embryo found ventral to the spinal cord). Connects centrally with the dorsal horn of the spinal cord.
* '''spinal nerve''' mixed nerve (motor and sensory) arising as latera pairs at each vertebral segmental level.
* '''sonic hedgehog''' (=shh) secreted growth factor that binds patched (ptc) receptor on cell membrane. SHH function is different for different tissues in the embryo. In the nervous system, it is secreted by the notochord, ventralizes the neural tube, inducing the floor plate and motor neurons.
* '''sulcus''' (L. furrow) groove
* '''sulcus limitans''' longitudinal lateral groove in neural tube approx. midway between roofplate and floorplate. Groove divides alar (dorsal) and basal (ventral) plate regions.
* '''sympathetic ganglia'''-
* '''telencephalon''' the cranial portion of forebrain after it divides into 2 parts in the 5 secondary vesicle brain (week 5). (cavity- lateral ventricles and some of 3rd ventricle) Forms the cerebral hemispheres in the adult brain. (sc-My-Met-Mes-Di-'''Tel''')
* '''thalamus''' (G. ''thalamos''= bedchamber) cns nucleus, lateral to 3rd ventricle, paired (pl thalami).
* '''transcription factor''' a factor (protein or protein with steroid) that binds to DNA to alter gene expression, usually to activate. (eg steroid hormone+receptor, Retinoic acid+Receptor, Hox, Pax, Lim, Nkx-2.2)
* '''trigeminal ganglion''' (=cranial nerve V, CN V) first arch ganglion, very large and has 3 portions.
* '''vagal ganglion- '''(=cranial nerve X, CN X) fourth and sixth arch ganglion, innervates the viscera and heart.
* '''ventricles''' the fluid-filled interconnected cavity system with the brain. Fluid (cerebrospinal fluid, CSF) is generated by the specialized vascular network, the choroid plexus. The ventricles are directly connected to the spinal canal (within the spinal cord).
* '''ventricular zone''' Neuroepithelial cell layer of neural tube closest to lumen. Neuroepithelial cells generate neurons, glia and ependymal cells. ('''Ven'''-Man-Mar-CP)
* '''vestibulocochlear nerve''' (=cranial nerve VIII, CN VIII, also called statoacoustic)
* '''white matter''' - neural regions containing processes (axons) of neurons. In the brain it is the inner layer, in the spinal cord it is outer layer. (see grey matter)

Latest revision as of 13:48, 7 December 2020

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Cite this page: Hill, M.A. (2026, August 16) Embryology Neural System Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Neural_System_Development

Neural Development Journal - https://neuraldevelopment.biomedcentral.com

Draft page - Neural System - Molecular

2020

Micali N, Kim SK, Diaz-Bustamante M, Stein-O'Brien G, Seo S, Shin JH, Rash BG, Ma S, Wang Y, Olivares NA, Arellano JI, Maynard KR, Fertig EJ, Cross AJ, Bürli RW, Brandon NJ, Weinberger DR, Chenoweth JG, Hoeppner DJ, Sestan N, Rakic P, Colantuoni C & McKay RD. (2020). Variation of Human Neural Stem Cells Generating Organizer States In Vitro before Committing to Cortical Excitatory or Inhibitory Neuronal Fates. Cell Rep , 31, 107599. PMID: 32375049 DOI.

Variation of Human Neural Stem Cells Generating Organizer States In Vitro before Committing to Cortical Excitatory or Inhibitory Neuronal Fates

Better understanding of the progression of neural stem cells (NSCs) in the developing cerebral cortex is important for modeling neurogenesis and defining the pathogenesis of neuropsychiatric disorders. Here, we use RNA sequencing, cell imaging, and lineage tracing of mouse and human in vitro NSCs and monkey brain sections to model the generation of cortical neuronal fates. We show that conserved signaling mechanisms regulate the acute transition from proliferative NSCs to committed glutamatergic excitatory neurons. As human telencephalic NSCs develop from pluripotency in vitro, they transition through organizer states that spatially pattern the cortex before generating glutamatergic precursor fates. NSCs derived from multiple human pluripotent lines vary in these early patterning states, leading differentially to dorsal or ventral telencephalic fates. This work furthers systematic analyses of the earliest patterning events that generate the major neuronal trajectories of the human telencephalon. Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved. KEYWORDS: BMP; EGFR; FGF2; brain organizer; glutamatergic neurons; human iPSC variation; inhibitory neurons; neural stem cell; neural transcriptional dynamics; neurogenesis; neuronal trajectory variation; patterning of the cortex PMID: 32375049 DOI: 10.1016/j.celrep.2020.107599


UNSW Embryology Links

  • Animal Neural Development - A number of different animal models of neural development, both normal and abnormal, have been established. Mouse | Pig | Rabbit


brain museum - histology images from different species http://www.brainmuseum.org/Specimens/index.html

Human Central Nervous System Development

Joseph Altman and Shirley A. Bayer

http://neurondevelopment.org

http://neurondevelopment.org

Atlas of Human Central Nervous System Development

  • The Spinal Cord from Gestational Week 4 to the 4th Postnatal Month

Shirley A . Bayer and Joseph Altman CRC Press 2002 Print ISBN: 978-0-8493-1420-9 eBook ISBN: 978-1-4200-4018-0 http://www.crcnetbase.com/doi/book/10.1201/9781420040180

  • The Human Brain During the Third Trimester

Shirley A . Bayer and Joseph Altman CRC Press 2003 Print ISBN: 978-0-8493-1421-6 eBook ISBN: 978-0-203-49494-3 http://www.crcnetbase.com/doi/book/10.1201/9780203494943

  • The Human Brain During the Second Trimester

Shirley A . Bayer and Joseph Altman CRC Press 2005 Print ISBN: 978-0-8493-1422-3 eBook ISBN: 978-0-203-50748-3 http://www.crcnetbase.com/doi/book/10.1201/9780203507483

  • The Human Brain During the Late First Trimester

Shirley A . Bayer and Joseph Altman CRC Press 2006 Print ISBN: 978-0-8493-1423-0 eBook ISBN: 978-1-4200-0327-7 http://www.crcnetbase.com/doi/book/10.1201/9781420003277

  • The Human Brain During the Early First Trimester

Shirley A . Bayer and Joseph Altman CRC Press 2007 Print ISBN: 978-0-8493-1424-7 eBook ISBN: 978-1-4200-0328-4 http://www.crcnetbase.com/doi/book/10.1201/9781420003284

2019

Zhu Y, Crowley SC, Latimer AJ, Lewis GM, Nash R & Kucenas S. (2019). Migratory Neural Crest Cells Phagocytose Dead Cells in the Developing Nervous System. Cell , 179, 74-89.e10. PMID: 31495570 DOI.

During neural tube closure and spinal cord development, many cells die in both the central and peripheral nervous systems (CNS and PNS, respectively). However, myeloid-derived professional phagocytes have not yet colonized the trunk region during early neurogenesis. How apoptotic cells are removed from this region during these stages remains largely unknown. Using live imaging in zebrafish, we demonstrate that neural crest cells (NCCs) respond rapidly to dying cells and phagocytose cellular debris around the neural tube. Additionally, NCCs have the ability to enter the CNS through motor exit point transition zones and clear debris in the spinal cord. Surprisingly, NCCs phagocytosis mechanistically resembles macrophage phagocytosis and their recruitment toward cellular debris is mediated by interleukin-1β. Taken together, our results reveal a role for NCCs in phagocytosis of debris in the developing nervous system before the presence of professional phagocytes.

Trush O, Liu C, Han X, Nakai Y, Takayama R, Murakawa H, Carrillo JA, Takechi H, Hakeda-Suzuki S, Suzuki T & Sato M. (2019). N-cadherin orchestrates self-organization of neurons within a columnar unit in the Drosophila medulla. J. Neurosci. , , . PMID: 31175213 DOI. neural fly

  • N-cadherin orchestrates self-organization of neurons within a columnar unit in the Drosophila medulla "The columnar structure is a basic unit of the brain, but its developmental mechanism remains unknown. The medulla, the largest ganglion of the fly visual center, provides a unique opportunity to reveal the mechanisms of three-dimensional organization of the columns. We reveal that column formation is initiated by three core neurons that establish distinct concentric domains within a column. We demonstrate the in vivo evidence of N-cadherin-dependent differential adhesion among the core columnar neurons within a column along a two-dimensional layer in the larval medulla. The two-dimensional larval columns evolve to form three distinct layers in the pupal medulla. We propose the presence of mutual interactions among the three layers during formation of the three-dimensional structures of the medulla columns." neural

2018

Caspases and matrix metalloproteases facilitate collective behavior of non-neural ectoderm after hindbrain neuropore closure

BMC Dev Biol. 2018 Jul 31;18(1):17. doi: 10.1186/s12861-018-0175-3.

Shinotsuka N1, Yamaguchi Y2,3, Nakazato K4, Matsumoto Y1, Mochizuki A4,5, Miura M6.

Abstract BACKGROUND: Mammalian brain is formed through neural tube closure (NTC), wherein both ridges of opposing neural folds are fused in the midline and remodeled in the roof plate of the neural tube and overlying non-neural ectodermal layer. Apoptosis is widely observed from the beginning of NTC at the neural ridges and is crucial for the proper progression of NTC, but its role after the closure remains less clear.

RESULTS: Here, we conducted live-imaging analysis of the mid-hindbrain neuropore (MHNP) closure and revealed unexpected collective behavior of cells surrounding the MHNP. The cells first gathered to the closing point and subsequently relocated as if they were released from the point. Inhibition of caspases or matrix metalloproteases with chemical inhibitors impaired the cell relocation.

CONCLUSIONS: These lines of evidence suggest that apoptosis-mediated degradation of extracellular matrix might facilitate the final process of neuropore closure.

KEYWORDS: Apoptosis; Caspases; Live-imaging; Matrix metalloproteases; Neural tube closure PMID: 30064364 PMCID: PMC6069860 DOI: 10.1186/s12861-018-0175-3

Nervous System Regionalization Entails Axial Allocation before Neural Differentiation

Cell. 2018 Oct 13. pii: S0092-8674(18)31252-2. doi: 10.1016/j.cell.2018.09.040. [Epub ahead of print]

Metzis V1, Steinhauser S1, Pakanavicius E1, Gouti M2, Stamataki D1, Ivanovitch K1, Watson T1, Rayon T1, Mousavy Gharavy SN1, Lovell-Badge R1, Luscombe NM3, Briscoe J4. Author information Abstract Neural induction in vertebrates generates a CNS that extends the rostral-caudal length of the body. The prevailing view is that neural cells are initially induced with anterior (forebrain) identity; caudalizing signals then convert a proportion to posterior fates (spinal cord). To test this model, we used chromatin accessibility to define how cells adopt region-specific neural fates. Together with genetic and biochemical perturbations, this identified a developmental time window in which genome-wide chromatin-remodeling events preconfigure epiblast cells for neural induction. Contrary to the established model, this revealed that cells commit to a regional identity before acquiring neural identity. This "primary regionalization" allocates cells to anterior or posterior regions of the nervous system, explaining how cranial and spinal neurons are generated at appropriate axial positions. These findings prompt a revision to models of neural induction and support the proposed dual evolutionary origin of the vertebrate CNS. KEYWORDS: ATAC-seq; CDX; WNT signaling; chromatin; computational genomics; embryonic development; gene regulation; neural induction; spinal cord; stem cells and development PMID: 30343898 DOI: 10.1016/j.cell.2018.09.040


2017

Molecular and cellular reorganization of neural circuits in the human lineage

Science. 2017 Nov 24;358(6366):1027-1032. doi: 10.1126/science.aan3456.

Sousa AMM1, Zhu Y1, Raghanti MA2, Kitchen RR3,4, Onorati M1,5, Tebbenkamp ATN1, Stutz B6, Meyer KA1, Li M1, Kawasawa YI1,7, Liu F1, Perez RG8, Mele M8, Carvalho T8, Skarica M1, Gulden FO1, Pletikos M1, Shibata A1, Stephenson AR2, Edler MK2, Ely JJ9, Elsworth JD4, Horvath TL1,6, Hof PR10, Hyde TM11, Kleinman JE11, Weinberger DR11, Reimers M12, Lifton RP13,14,15, Mane SM16, Noonan JP13, State MW17, Lein ES18, Knowles JA19, Marques-Bonet T8,20,21, Sherwood CC22, Gerstein MB3, Sestan N23,4,6,13,24.


Abstract To better understand the molecular and cellular differences in brain organization between human and nonhuman primates, we performed transcriptome sequencing of 16 regions of adult human, chimpanzee, and macaque brains. Integration with human single-cell transcriptomic data revealed global, regional, and cell-type-specific species expression differences in genes representing distinct functional categories. We validated and further characterized the human specificity of genes enriched in distinct cell types through histological and functional analyses, including rare subpallial-derived interneurons expressing dopamine biosynthesis genes enriched in the human striatum and absent in the nonhuman African ape neocortex. Our integrated analysis of the generated data revealed diverse molecular and cellular features of the phylogenetic reorganization of the human brain across multiple levels, with relevance for brain function and disease. PMID: 29170230

Mouse Fgf8-Cre-LacZ lineage analysis defines the territory of the postnatal mammalian isthmus

J Comp Neurol. 2017 Aug 15;525(12):2782-2799. doi: 10.1002/cne.24242. Epub 2017 May 30.

Watson C1, Shimogori T2, Puelles L3.

Abstract

The isthmus is recognized as the most rostral segment of the hindbrain in non-mammalian vertebrates. In mammalian embryos, transient Fgf8 expression defines the developing isthmic region, lying between the midbrain and the first rhombomere, but there has been uncertainty about the existence of a distinct isthmic segment in postnatal mammals. We attempted to find if the region of early embryonic Fgf8 expression (which is considered to involve the entire extent of the prospective isthmus initially) might help to identify the boundaries of the isthmus in postnatal animals. By creating an Fgf8-Cre-LacZ lineage in mice, we were able to show that Fgf8-Cre reporter expression in postnatal mice is present in the same nuclei that characterize the isthmic region in birds. The 'signature' isthmic structures in birds include the trochlear nucleus, the dorsal raphe nucleus, the microcellular tegmental nuclei, the pedunculotegmental nucleus, the vermis of the cerebellum, rostral parts of the parabrachial complex and locus coeruleus, and the caudal parts of the substantia nigra and VTA. We found that all of these structures were labeled with the Fgf8-Cre reporter in the mouse brain, and we conclude that the isthmus is a distinct segment of the mammalian brain lying caudal to the midbrain and rostral to rhombomere 1 of the hindbrain. © 2017 Wiley Periodicals, Inc.

KEYWORDS: Fgf8; Isthmus; RRID:AB_2313764; cerebellum; midbrain; rhombomere PMID: 28510270 DOI: 10.1002/cne.24242

2015

First trimester size charts of embryonic brain structures

Hum Reprod. 2014 Feb;29(2):201-7. doi: 10.1093/humrep/det406. Epub 2013 Nov 28.

Gijtenbeek M1, Bogers H, Groenenberg IA, Exalto N, Willemsen SP, Steegers EA, Eilers PH, Steegers-Theunissen RP.

Abstract

STUDY QUESTION: Can reliable size charts of human embryonic brain structures be created from three-dimensional ultrasound (3D-US) visualizations? SUMMARY ANSWER: Reliable size charts of human embryonic brain structures can be created from high-quality images. WHAT IS KNOWN ALREADY: Previous studies on the visualization of both the cavities and the walls of the brain compartments were performed using 2D-US, 3D-US or invasive intrauterine sonography. However, the walls of the diencephalon, mesencephalon and telencephalon have not been measured non-invasively before. Last-decade improvements in transvaginal ultrasound techniques allow a better visualization and offer the tools to measure these human embryonic brain structures with precision. STUDY DESIGN, SIZE, DURATION: This study is embedded in a prospective periconceptional cohort study. A total of 141 pregnancies were included before the sixth week of gestation and were monitored until delivery to assess complications and adverse outcomes. PARTICIPANTS/MATERIALS, SETTING, METHODS: For the analysis of embryonic growth, 596 3D-US scans encompassing the entire embryo were obtained from 106 singleton non-malformed live birth pregnancies between 7(+0) and 12(+6) weeks' gestational age (GA). Using 4D View (3D software) the measured embryonic brain structures comprised thickness of the diencephalon, mesencephalon and telencephalon, and the total diameter of the diencephalon and mesencephalon. MAIN RESULTS AND THE ROLE OF CHANCE: Of 596 3D scans, 161 (27%) high-quality scans of 79 pregnancies were eligible for analysis. The reliability of all embryonic brain structure measurements, based on the intra-class correlation coefficients (ICCs) (all above 0.98), was excellent. Bland-Altman plots showed moderate agreement for measurements of the telencephalon, but for all other measurements the agreement was good. Size charts were constructed according to crown-rump length (CRL). LIMITATIONS, REASONS FOR CAUTION: The percentage of high-quality scans suitable for analysis of these brain structures was low (27%). WIDER IMPLICATIONS OF THE FINDINGS: 

The size charts of human embryonic brain structures can be used to study normal and abnormal development of brain development in future. Also, the effects of periconceptional maternal exposures, such as folic acid supplement use and smoking, on human embryonic brain development can be a topic of future research.

STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the Department of Obstetrics and Gynaecology of the Erasmus University Medical Center. M.G. was supported by an additional grant from the Sophia Foundation for Medical Research (SSWO grant number 644). No competing interests are declared. KEYWORDS: embryo development; embryology; pregnancy; prenatal diagnosis; ultrasound

PMID 24287820

Cell cycle regulation of proliferation versus differentiation in the central nervous system

Cell Tissue Res. 2015 Jan;359(1):187-200. doi: 10.1007/s00441-014-1895-8. Epub 2014 May 25.

Hardwick LJ1, Ali FR, Azzarelli R, Philpott A.

Abstract

Formation of the central nervous system requires a period of extensive progenitor cell proliferation, accompanied or closely followed by differentiation; the balance between these two processes in various regions of the central nervous system gives rise to differential growth and cellular diversity. The correlation between cell cycle lengthening and differentiation has been reported across several types of cell lineage and from diverse model organisms, both in vivo and in vitro. Furthermore, different cell fates might be determined during different phases of the preceding cell cycle, indicating direct cell cycle influences on both early lineage commitment and terminal cell fate decisions. Significant advances have been made in the last decade and have revealed multi-directional interactions between the molecular machinery regulating the processes of cell proliferation and neuronal differentiation. Here, we first introduce the modes of proliferation in neural progenitor cells and summarise evidence linking cell cycle length and neuronal differentiation. Second, we describe the manner in which components of the cell cycle machinery can have additional and, sometimes, cell-cycle-independent roles in directly regulating neurogenesis. Finally, we discuss the way that differentiation factors, such as proneural bHLH proteins, can promote either progenitor maintenance or differentiation according to the cellular environment. These intricate connections contribute to precise coordination and the ultimate division versus differentiation decision. PMID 24859217

Genes expressed in mouse cortical progenitors are enriched in Pax, Lhx, and Sox transcription factor putative binding sites

Brain Res. 2015 Dec 23. pii: S0006-8993(15)00961-0. doi: 10.1016/j.brainres.2015.12.022. [Epub ahead of print]

Bery A1, Mérot Y2, Rétaux S3.

Abstract

Considerable progress has been made in the understanding of molecular and cellular mechanisms controlling the development of the mammalian cortex. The proliferative and neurogenic properties of cortical progenitors located in the ventricular germinal zone start being understood. Little is known however on the cis-regulatory control that finely tunes gene expression in these progenitors. Here, we undertook an in silico-based approach to address this question, followed by some functional validation. Using the Eurexpress database, we established a list of 30 genes specifically expressed in the cortical germinal zone, we selected mouse/human conserved non-coding elements (CNEs) around these genes and we performed motif-enrichment search in these CNEs. We found an over-representation of motifs corresponding to binding sites for Pax, Sox, and Lhx transcription factors, often found as pairs and located within 100bp windows. A small subset of CNEs (n=7) was tested for enhancer activity, by ex-vivo and in utero electroporation assays. Two showed strong enhancer activity in the germinal zone progenitors. Mutagenesis experiments on a selected CNE showed the functional importance of the Pax, Sox, and Lhx TFBS for conferring enhancer activity to the CNE. Overall, from a cis-regulatory viewpoint, our data suggest an input from Pax, Sox and Lhx transcription factors to orchestrate corticogenesis. These results are discussed with regards to the known functional roles of Pax6, Sox2 and Lhx2 in cortical development. Copyright © 2015 Elsevier B.V. All rights reserved. KEYWORDS: Enhancer activity; Lhx2; Motif search; Mutagenesis; Non-coding regulatory element; in vivo electroporation

PMID 26721689

Development of the vertebrate tailbud

Wiley Interdiscip Rev Dev Biol. 2015 Jan-Feb;4(1):33-44. doi: 10.1002/wdev.163. Epub 2014 Nov 10.

Beck CW1.

Abstract

The anatomical tailbud is a defining feature of all embryonic chordates, including vertebrates that do not end up with a morphological tail. Due to its seamless continuity with trunk tissues, the tailbud is often overlooked as a mere extension of the body axis; however, the formation of the tail from the tailbud undoubtedly involves unique and distinct mechanisms for forming axial tissues, such as the secondary neurulation process that generates the tailbud-derived spinal cord. Tailbud formation in the frog Xenopus laevis has been demonstrated to involve interaction of three posterior regions of the embryo that first come into alignment at the end of gastrulation, and molecular models for tailbud outgrowth and patterning have been proposed. While classical studies of other vertebrate models, such as the chicken, initially appeared to draw incompatible conclusions, molecular studies have subsequently shown the involvement of at least some similar genetic pathways. Finally, there is an emerging consensus that at least some vertebrate tailbud cells are multipotent progenitors with the ability to form tissues normally derived from different germ layers- a trait normally associated with regeneration of complex appendages, or stem-like cells. © 2014 Wiley Periodicals, Inc.

PMID 25382697

http://onlinelibrary.wiley.com/doi/10.1002/wdev.163/full

Cellular basis of neuroepithelial bending during mouse spinal neural tube closure

Dev Biol. 2015 Aug 15;404(2):113-24. doi: 10.1016/j.ydbio.2015.06.003. Epub 2015 Jun 12.

McShane SG1, Molè MA1, Savery D1, Greene ND1, Tam PP2, Copp AJ3.

Abstract

Bending of the neural plate at paired dorsolateral hinge points (DLHPs) is required for neural tube closure in the spinal region of the mouse embryo. As a step towards understanding the morphogenetic mechanism of DLHP development, we examined variations in neural plate cellular architecture and proliferation during closure. Neuroepithelial cells within the median hinge point (MHP) contain nuclei that are mainly basally located and undergo relatively slow proliferation, with a 7h cell cycle length. In contrast, cells in the dorsolateral neuroepithelium, including the DLHP, exhibit nuclei distributed throughout the apico-basal axis and undergo rapid proliferation, with a 4h cell cycle length. As the neural folds elevate, cell numbers increase to a greater extent in the dorsolateral neural plate that contacts the surface ectoderm, compared with the more ventromedial neural plate where cells contact paraxial mesoderm and notochord. This marked increase in dorsolateral cell number cannot be accounted for solely on the basis of enhanced cell proliferation in this region. We hypothesised that neuroepithelial cells may translocate in a ventral-to-dorsal direction as DLHP formation occurs, and this was confirmed by vital cell labelling in cultured embryos. The translocation of cells into the neural fold, together with its more rapid cell proliferation, leads to an increase in cell density dorsolaterally compared with the more ventromedial neural plate. These findings suggest a model in which DLHP formation may proceed through 'buckling' of the neuroepithelium at a dorso-ventral boundary marked by a change in cell-packing density. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved. KEYWORDS: Cell proliferation; Embryo; Mouse; Neural tube closure; Neurulation

PMID 26079577

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4528075/

A Functional Perspective on the Embryology and Anatomy of the Cerebral Blood Supply

J Stroke. 2015 May;17(2):144-58. doi: 10.5853/jos.2015.17.2.144. Epub 2015 May 29.

Menshawi K1, Mohr JP1, Gutierrez J1.

Abstract

The anatomy of the arterial system supplying blood to the brain can influence the development of arterial disease such as aneurysms, dolichoectasia and atherosclerosis. As the arteries supplying blood to the brain develop during embryogenesis, variation in their anatomy may occur and this variation may influence the development of arterial disease. Angiogenesis, which occurs mainly by sprouting of parent arteries, is the first stage at which variations can occur. At day 24 of embryological life, the internal carotid artery is the first artery to form and it provides all the blood required by the primitive brain. As the occipital region, brain stem and cerebellum enlarge; the internal carotid supply becomes insufficient, triggering the development of the posterior circulation. At this stage, the posterior circulation consists of a primitive mesh of arterial networks that originate from projection of penetrators from the distal carotid artery and more proximally from carotid-vertebrobasilar anastomoses. These anastomoses regress when the basilar artery and the vertebral arteries become independent from the internal carotid artery, but their persistence is not uncommon in adults (e.g., persistent trigeminal artery). Other common remnants of embryological development include fenestration or duplication (most commonly of the basilar artery), hypoplasia (typically of the posterior communicating artery) or agenesis (typically of the anterior communicating artery). Learning more about the hemodynamic consequence that these variants may have on the brain territories they supply may help understand better the underlying physiopathology of cerebral arterial remodeling and stroke in patients with these variants. KEYWORDS: Arterial variants; Cerebral arteries; Circle of willis; Embryology; Remodeling; Stroke

PMID 26060802

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

http://synapse.koreamed.org/search.php?where=aview&id=10.5853/jos.2015.17.2.144&code=1183JOS&vmode=FT


2014

A conserved role for non-neural ectoderm cells in early neural development

Development. 2014 Nov;141(21):4127-38. doi: 10.1242/dev.107425. Epub 2014 Oct 1.

Cajal M1, Creuzet SE2, Papanayotou C1, Sabéran-Djoneidi D1, Chuva de Sousa Lopes SM3, Zwijsen A4, Collignon J1, Camus A5.

Abstract

During the early steps of head development, ectodermal patterning leads to the emergence of distinct non-neural and neural progenitor cells. The induction of the preplacodal ectoderm and the neural crest depends on well-studied signalling interactions between the non-neural ectoderm fated to become epidermis and the prospective neural plate. By contrast, the involvement of the non-neural ectoderm in the morphogenetic events leading to the development and patterning of the central nervous system has been studied less extensively. Here, we show that the removal of the rostral non-neural ectoderm abutting the prospective neural plate at late gastrulation stage leads, in mouse and chick embryos, to morphological defects in forebrain and craniofacial tissues. In particular, this ablation compromises the development of the telencephalon without affecting that of the diencephalon. Further investigations of ablated mouse embryos established that signalling centres crucial for forebrain regionalization, namely the axial mesendoderm and the anterior neural ridge, form normally. Moreover, changes in cell death or cell proliferation could not explain the specific loss of telencephalic tissue. Finally, we provide evidence that the removal of rostral tissues triggers misregulation of the BMP, WNT and FGF signalling pathways that may affect telencephalon development. This study opens new perspectives on the role of the neural/non-neural interface and reveals its functional relevance across higher vertebrates. © 2014. Published by The Company of Biologists Ltd. KEYWORDS: Apoptosis; Chick; Embryo; Forebrain patterning; Mouse; Signalling centre; Telencephalon; Vertebrates

PMID 25273086

Syndecan 4 interacts genetically with Vangl2 to regulate neural tube closure and planar cell polarity

Development. 2013 Jul;140(14):3008-17. doi: 10.1242/dev.091173. Epub 2013 Jun 12.

Escobedo N1, Contreras O, Muñoz R, Farías M, Carrasco H, Hill C, Tran U, Pryor SE, Wessely O, Copp AJ, Larraín J.

Abstract

Syndecan 4 (Sdc4) is a cell-surface heparan sulfate proteoglycan (HSPG) that regulates gastrulation, neural tube closure and directed neural crest migration in Xenopus development. To determine whether Sdc4 participates in Wnt/PCP signaling during mouse development, we evaluated a possible interaction between a null mutation of Sdc4 and the loop-tail allele of Vangl2. Sdc4 is expressed in multiple tissues, but particularly in the non-neural ectoderm, hindgut and otic vesicles. Sdc4;Vangl2(Lp) compound mutant mice have defective spinal neural tube closure, disrupted orientation of the stereocilia bundles in the cochlea and delayed wound healing, demonstrating a strong genetic interaction. In Xenopus, co-injection of suboptimal amounts of Sdc4 and Vangl2 morpholinos resulted in a significantly greater proportion of embryos with defective neural tube closure than each individual morpholino alone. To probe the mechanism of this interaction, we overexpressed or knocked down Vangl2 function in HEK293 cells. The Sdc4 and Vangl2 proteins colocalize, and Vangl2, particularly the Vangl2(Lp) mutant form, diminishes Sdc4 protein levels. Conversely, Vangl2 knockdown enhances Sdc4 protein levels. Overall HSPG steady-state levels were regulated by Vangl2, suggesting a molecular mechanism for the genetic interaction in which Vangl2(Lp/+) enhances the Sdc4-null phenotype. This could be mediated via heparan sulfate residues, as Vangl2(Lp/+) embryos fail to initiate neural tube closure and develop craniorachischisis (usually seen only in Vangl2(Lp/Lp)) when cultured in the presence of chlorate, a sulfation inhibitor. These results demonstrate that Sdc4 can participate in the Wnt/PCP pathway, unveiling its importance during neural tube closure in mammalian embryos. KEYWORDS: Neural tube defects; Proteoglycans; Wnt planar cell polarity

PMID 23760952

Open Access

http://dev.biologists.org/content/140/14/3008.full?sid=38c9b5ee-04c8-4f9c-9e8f-f29d56dd1d46

Secondary neurulation of human embryos: morphological changes and the expression of neuronal antigens

Childs Nerv Syst. 2014 Jan;30(1):73-82. doi: 10.1007/s00381-013-2192-7. Epub 2013 Jun 13.

Yang HJ, Lee DH, Lee YJ, Chi JG, Lee JY, Phi JH, Kim SK, Cho BK, Wang KC. Author information

Abstract PURPOSE: The morphological changes and expression patterns of neuronal antigens of human embryos, obtained from the therapeutic termination of pregnancy or from surgical procedures, were analyzed in order to characterize the secondary neurulation. METHODS: A total of 21 human embryos from Carnegie stages 12 to 23 and two fetuses in early stages were studied. The markers used for immunohistochemical study were neural cell adhesion molecule (N-CAM), neuronal nuclear antigen (NeuN), neurofilament-associated protein (3A10), synaptophysin, and glial fibrillary acidic protein (GFAP). RESULTS: The formation of the caudal neural tube to the tip of the caudal portion of the embryo was finished at stage 17. The postcloacal gut had completely disappeared at stage 18, and multiple cavities of the caudal neural tube were clearly visible. The caudal portion of the neural tube showed findings suggestive of involution at stage 19. The expression patterns of neuronal antigens were as follows: N-CAM and NeuN showed immunoreactivity at the germinal layer of the spinal cord at stages 17 and 18. Neurofilament-associated protein (3A10) showed persistent immunoreactivity at the caudal cell mass and notochord during the observation period, along with the spinal cord, and the positive reactions were mainly located at the dorsal white matter at stage 17. Synaptophysin showed a weak positive reaction at the caudal cell mass and notochord at stages 13 and 14, evident by staining observed at the spinal cord at stages 15 and 16. There was no definite positive reaction for GFAP. CONCLUSIONS: These characteristic patterns might be helpful for the understanding of human congenital anomalies involving secondary neurulation processes. PMID 23760472

2013

The longitudinal growth of the neuromeres and the resulting brain in the human embryo

O'Rahilly R. and Müller F. The longitudinal growth of the neuromeres and the resulting brain in the human embryo. (2013) Cells Tissues Organs. 197(3):178-95. doi: 10.1159/000343170. PMID 23183269.

Cells Tissues Organs. 2013;197(3):178-95. doi: 10.1159/000343170. Epub 2012 Nov 24.

O'Rahilly R, Müller F. Author information

Abstract

The growth of the human brain during the embryonic period was assessed in terms of longitudinal measurements in staged embryos. Precise graphic reconstructions prepared by the onerous point-plotting method were considered to be the most reliable, and 23 were examined in detail. A distinction is necessary between measurements of the brain (cerebral diameters) and those of the skull (osseous diameters), and also between those of the folded brain in situ, studied here, and the later relatively straightened brain. Longitudinal measurements were made of individual neuromeres and their successors in steps (neuromeric lengths). The sum of the neuromeric measurements at any given stage provides the total neuromeric length (TNL) of the folded brain in situ at that stage and it increases in keeping with the greatest length (GL) of the embryo. At stages 16-19, however, the neuromeric length of the brain may exceed the GL. From stage 20 onwards the body length increases more rapidly compared with the length of the brain. The most cephalic neuromere is the telencephalon medium, abbreviated T1 here. The cerebral hemispheres are derived from it, although they are not neuromeres. The hemispheres soon extend rostrally beyond the limit of T1 by an amount that is here designated T2, and that indicates the growth of the telencephalon rostral to the commissural plate, which is the site of the future corpus callosum. Further laterally, the hemispheric length (future fronto-occipital diameter) increases rapidly, as does also the bitemporal (biparietal) diameter. At the end of the embryonic period these diameters are one fourth to one fifth of the head circumference. Additional neuromeric information becomes manifest when the measurements are calculated as percentages of the total length of the brain. The rhombencephalon decreases considerably, diencephalon 2 increases greatly, whereas diencephalon 1 diminishes, and the cerebral hemispheres enlarge massively. In addition, specific neuromeres or subdivisions come to occupy relatively more or relatively less of the total. Three periods were found during which individual neuromeres acquire their maximal or minimal lengths: the maximal absolute lengths were in period 3, whereas the maximal and minimal percentage lengths were in periods 1 and 3. The various neuromeric changes are considered to be related to alterations in functional development. Finally, in furtherance of establishing continuity in prenatal data, comparisons were effected between embryonic and fetal measurements. Copyright © 2012 S. Karger AG, Basel.

PMID 23183269

Neural induction and early patterning in vertebrates

Wiley Interdiscip Rev Dev Biol. 2013 Jul;2(4):479-98. doi: 10.1002/wdev.90. Epub 2012 Oct 15.

Ozair MZ, Kintner C, Brivanlou AH. Source Laboratory of Molecular Vertebrate Embryology, The Rockefeller University, New York, NY, USA.

Abstract

In vertebrates, the development of the nervous system is triggered by signals from a powerful 'organizing' region of the early embryo during gastrulation. This phenomenon--neural induction--was originally discovered and given conceptual definition by experimental embryologists working with amphibian embryos. Work on the molecular circuitry underlying neural induction, also in the same model system, demonstrated that elimination of ongoing transforming growth factor-β (TGFβ) signaling in the ectoderm is the hallmark of anterior neural-fate acquisition. This observation is the basis of the 'default' model of neural induction. Endogenous neural inducers are secreted proteins that act to inhibit TGFβ ligands in the dorsal ectoderm. In the ventral ectoderm, where the signaling ligands escape the inhibitors, a non-neural fate is induced. Inhibition of the TGFβ pathway has now been demonstrated to be sufficient to directly induce neural fate in mammalian embryos as well as pluripotent mouse and human embryonic stem cells. Hence the molecular process that delineates neural from non-neural ectoderm is conserved across a broad range of organisms in the evolutionary tree. The availability of embryonic stem cells from mouse, primates, and humans will facilitate further understanding of the role of signaling pathways and their downstream mediators in neural induction in vertebrate embryos. Copyright © 2012 Wiley Periodicals, Inc.

PMID 24014419

Developmental mechanisms directing early anterior forebrain specification in vertebrates

Cell Mol Life Sci. 2013 Oct;70(20):3739-52. doi: 10.1007/s00018-013-1269-5. Epub 2013 Feb 9.

Andoniadou CL, Martinez-Barbera JP. Source Birth Defects Research Centre, UCL Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, UK. Abstract Research from the last 15 years has provided a working model for how the anterior forebrain is induced and specified during the early stages of embryogenesis. This model relies on three basic processes: (1) induction of the neural plate from naive ectoderm requires the inhibition of BMP/TGFβ signaling; (2) induced neural tissue initially acquires an anterior identity (i.e., anterior forebrain); (3) maintenance and expansion of the anterior forebrain depends on the antagonism of posteriorizing signals that would otherwise transform this tissue into posterior neural fates. In this review, we present a historical perspective examining some of the significant experiments that have helped to delineate this molecular model. In addition, we discuss the function of the relevant tissues that act prior to and during gastrulation to ensure proper anterior forebrain formation. Finally, we elaborate data, mainly obtained from the analyses of mouse mutants, supporting a role for transcriptional repressors in the regulation of cell competence within the anterior forebrain. The aim of this review is to provide the reader with a general overview of the signals as well as the signaling centers that control the development of the anterior neural plate.

PMID 23397132


Cell cycle and lineage progression of neural progenitors in the ventricular-subventricular zones of adult mice

Proc Natl Acad Sci U S A. 2013 Mar 12;110(11):E1045-54. doi: 10.1073/pnas.1219563110. Epub 2013 Feb 21.

Ponti G, Obernier K, Guinto C, Jose L, Bonfanti L, Alvarez-Buylla A. Source Department of Neurological Surgery and The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA 94143, USA.

Abstract

Proliferating neural stem cells and intermediate progenitors persist in the ventricular-subventricular zone (V-SVZ) of the adult mammalian brain. This extensive germinal layer in the walls of the lateral ventricles is the site of birth of different types of interneurons destined for the olfactory bulb. The cell cycle dynamics of stem cells (B1 cells), intermediate progenitors (C cells), and neuroblasts (A cells) in the V-SVZ and the number of times these cells divide remain unknown. Using whole mounts of the walls of the lateral ventricles of adult mice and three cell cycle analysis methods using thymidine analogs, we determined the proliferation dynamics of B1, C, and A cells in vivo. Achaete-scute complex homolog (Ascl)1(+) C cells were heterogeneous with a cell cycle length (T(C)) of 18-25 h and a long S phase length (T(S)) of 14-17 h. After C cells, Doublecortin(+) A cells were the second-most common dividing cell type in the V-SVZ and had a T(C) of 18 h and T(S) of 9 h. Human glial fibrillary acidic protein (hGFAP)::GFP(+) B1 cells had a surprisingly short Tc of 17-18 h and a T(S) of 4 h. Progenitor population analysis suggests that following the initial division of B1 cells, C cells divide three times and A cells once, possibly twice. These data provide essential information on the dynamics of adult progenitor cell proliferation in the V-SVZ and how large numbers of new neurons continue to be produced in the adult mammalian brain. PMID 23431204

2012

2011

Proc Natl Acad Sci U S A. 2011 Aug 16;108(33):13776-81. Epub 2011 Jul 27.

Spatial and temporal second messenger codes for growth cone turning

Nicol X, Hong KP, Spitzer NC. Source Neurobiology Section, Division of Biological Sciences, Kavli Institute for Brain and Mind, University of California at San Diego, La Jolla, CA 92093, USA. xavier.nicol@inserm.fr

Abstract

Cyclic AMP (cAMP) and calcium are ubiquitous, interdependent second messengers that regulate a wide range of cellular processes. During development of neuronal networks they are critical for the first step of circuit formation, transducing signals required for axon pathfinding. Surprisingly, the spatial and temporal cAMP and calcium codes used by axon guidance molecules are unknown. Here, we identify characteristics of cAMP and calcium transients generated in growth cones during Netrin-1-dependent axon guidance. In filopodia, Netrin-1-dependent Deleted in Colorectal Cancer (DCC) receptor activation induces a transient increase in cAMP that causes a brief increase in calcium transient frequency. In contrast, activation of DCC in growth cone centers leads to a transient calcium-dependent cAMP increase and a sustained increase in frequency of calcium transients. We show that filopodial cAMP transients regulate spinal axon guidance in vitro and commissural axon pathfinding in vivo. These growth cone codes provide a basis for selective activation of specific downstream effectors.

PMID 21795610

The Zagreb Collection of human brains: a unique, versatile, but underexploited resource for the neuroscience community

Ann N Y Acad Sci. 2011 May;1225 Suppl 1:E105-30. doi: 10.1111/j.1749-6632.2011.05993.x.

Judaš M, Šimić G, Petanjek Z, Jovanov-Milošević N, Pletikos M, Vasung L, Vukšić M, Kostović I. Source University of Zagreb School of Medicine, Croatian Institute for Brain Research, Zagreb, Croatia. Abstract The Zagreb Collection of developing and adult human brains was founded in 1974 by Ivica Kostović and consists of 1,278 developing and adult human brains, including 610 fetal, 317 children, and 359 adult brains. It is one of the largest collections of developing human brains. The collection serves as a key resource for many focused research projects and has led to several seminal contributions on mammalian cortical development, such as the discovery of the transient fetal subplate zone and of early bilaminar synaptogenesis in the embryonic and fetal human cerebral cortex, and the first description of growing afferent pathways in the human fetal telencephalon. The Zagreb Collection also serves as a core resource for ever-growing networks of international collaboration and represents the starting point for many young investigators who now pursue independent research careers at leading international institutions. The Zagreb Collection, however, remains underexploited owing to a lack of adequate funding in Croatia. Funding could establish an online catalog of the collection and modern virtual microscopy scanning methods to make the collection internationally more accessible.

© 2011 New York Academy of Sciences.

PMID: 21599691 http://www.ncbi.nlm.nih.gov/pubmed/21599691

Plxdc2 is a mitogen for neural progenitors

PLoS One. 2011 Jan 21;6(1):e14565.

Miller-Delaney SF, Lieberam I, Murphy P, Mitchell KJ. Smurfit Institute of Genetics and Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.

Abstract

The development of different brain regions involves the coordinated control of proliferation and cell fate specification along and across the neuraxis. Here, we identify Plxdc2 as a novel regulator of these processes, using in ovo electroporation and in vitro cultures of mammalian cells. Plxdc2 is a type I transmembrane protein with some homology to nidogen and to plexins. It is expressed in a highly discrete and dynamic pattern in the developing nervous system, with prominent expression in various patterning centres. In the chick neural tube, where Plxdc2 expression parallels that seen in the mouse, misexpression of Plxdc2 increases proliferation and alters patterns of neurogenesis, resulting in neural tube thickening at early stages. Expression of the Plxdc2 extracellular domain alone, which can be cleaved and shed in vivo, is sufficient for this activity, demonstrating a cell non-autonomous function. Induction of proliferation is also observed in cultured embryonic neuroepithelial cells (ENCs) derived from E9.5 mouse neural tube, which express a Plxdc2-binding activity. These experiments uncover a direct molecular activity of Plxdc2 in the control of proliferation, of relevance in understanding the role of this protein in various cancers, where its expression has been shown to be altered. They also implicate Plxdc2 as a novel component of the network of signalling molecules known to coordinate proliferation and differentiation in the developing nervous system.

PMID: 21283688 http://www.ncbi.nlm.nih.gov/pubmed/21283688

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3024984

Plxdc2 transmembrane protein Plexin domain-containing 2. mouse Plxdc2 gene encodes a type I transmembrane protein of 530 amino acids, characterised by an extracellular region of weak nidogen homology and a plexin repeat or PSI domain, a domain found in several known axon guidance molecules.

Plxdc1 In the human, mouse and chick Plxdc2 has this one related gene.

Molecular Patterning "The midbrain-hindbrain boundary (MHB), which expresses Wnt1 and Fgf8, is one of several local signalling centres in the neuroepithelium which refines AP specification of the brain. DV patterning is influenced by the floor plate, which expresses ventralising factors including sonic hedgehog (Shh) and nodal and the roof plate at the dorsal midline, which expresses members of the BMP and Wnt families. Differential dorsal and ventral growth of the brain is also co-ordinated via a signalling cascade of Shh, FGF and Wnt activity."

2010

Developmental changes in cerebral grey and white matter volume from infancy to adulthood.

Int J Dev Neurosci. 2010 Oct;28(6):481-9. Epub 2010 Jun 30. Groeschel S, Vollmer B, King MD, Connelly A.

Radiology and Physics Unit, UCL Institute of Child Health, London, UK. s.groeschel@gmx.org Abstract

In order to quantify human brain development in vivo, high resolution magnetic resonance images of 158 normal subjects from infancy to young adulthood were studied (age range 3 months-30 years, 71 males, 87 females). Data were analysed using algorithms based on voxel-based morphometry (VBM) (an objective whole brain processing technique) to generate global volume measures of whole brain, grey matter (GM) and white matter (GM). Gender-specific development of WM and GM volumes is characterised using a piecewise polynomial growth curve model to account for the non-linear nature of human brain development, implemented using Markov chain Monte Carlo simulation. The statistical method employed in this study proved to be successful and robust in the characterisation of brain development. The resulting growth curve parameter estimates lead to the following observations: total brain volume is demonstrated to undergo an initial rapid spurt. The total GM volume peaks during childhood and decreases thereafter, whereas total WM volume increases up to young adulthood. Relative to brain size, GM decreases and WM increases markedly over this age range in a non-linear manner, resulting in an increasing WM-to-GM ratio over much of the observed age range. In addition, significant gender differences are found. In general, brain volume and total white and grey matter volume are larger in males than in females, with a time-dependent difference over the age range studied. Over part of the observed age range females tend to have more GM volume relative to brain size and lower WM-to-GM ratio than males. The presented findings should be taken into account when investigating physiological and pathological changes during brain development.

http://www.ncbi.nlm.nih.gov/pubmed/20600789

2009

Heterogeneity in subcortical brain development: A structural magnetic resonance imaging study of brain maturation from 8 to 30 years.

J Neurosci. 2009 Sep 23;29(38):11772-82.

Ostby Y, Tamnes CK, Fjell AM, Westlye LT, Due-Tønnessen P, Walhovd KB.

Center for the Study of Human Cognition, Department of Psychology, University of Oslo, Norway. ylva.ostby@psykologi.uio.no Abstract Brain development during late childhood and adolescence is characterized by decreases in gray matter (GM) and increases in white matter (WM) and ventricular volume. The dynamic nature of development across different structures is, however, not well understood, and the present magnetic resonance imaging study took advantage of a whole-brain segmentation approach to describe the developmental trajectories of 16 neuroanatomical volumes in the same sample of children, adolescents, and young adults (n = 171; range, 8-30 years). The cerebral cortex, cerebral WM, caudate, putamen, pallidum, accumbens area, hippocampus, amygdala, thalamus, brainstem, cerebellar GM, cerebellar WM, lateral ventricles, inferior lateral ventricles, third ventricle, and fourth ventricle were studied. The cerebral cortex was further analyzed in terms of lobar thickness and surface area. The results revealed substantial heterogeneity in developmental trajectories. GM decreased nonlinearly in the cerebral cortex and linearly in the caudate, putamen, pallidum, accumbens, and cerebellar GM, whereas the amygdala and hippocampus showed slight, nonlinear increases in GM volume. WM increased nonlinearly in both the cerebrum and cerebellum, with an earlier maturation in cerebellar WM. In addition to similarities in developmental trajectories within subcortical regions, our results also point to differences between structures within the same regions: among the basal ganglia, the caudate showed a weaker relationship with age than the putamen and pallidum, and in the cerebellum, differences were found between GM and WM development. These results emphasize the importance of studying a wide range of structural variables in the same sample, for a broader understanding of brain developmental principles.

http://www.ncbi.nlm.nih.gov/pubmed/19776264 http://www.jneurosci.org/cgi/content/full/29/38/11772

2008

Progressive loss of PAX6, TBR2, NEUROD and TBR1 mRNA gradients correlates with translocation of EMX2 to the cortical plate during human cortical development

Eur J Neurosci. 2008 Oct;28(8):1449-56.

Bayatti N, Sarma S, Shaw C, Eyre JA, Vouyiouklis DA, Lindsay S, Clowry GJ. Source Institute of Neuroscience, Newcastle University, Newcastle-upon-Tyne, UK.

Abstract

The transcription factors Emx2 and Pax6 are expressed in the proliferating zones of the developing rodent neocortex, and gradients of expression interact in specifying caudal and rostral identities. Pax6 is also involved in corticoneurogenesis, being expressed by radial glial progenitors that give rise to cells that also sequentially express Tbr2, NeuroD and Tbr1, genes temporally downstream of Pax6. In this study, using in situ hybridization, we analysed the expression of EMX2, PAX6, TBR2, NEUROD and TBR1 mRNA in the developing human cortex between 8 and 12 postconceptional weeks (PCW). EMX2 mRNA was expressed in the ventricular (VZ) and subventricular zones (SVZ), but also in the cortical plate, unlike in the rodent. However, gradients of expression were similar to that of the rodent at all ages studied. PAX6 mRNA expression was limited to the VZ and SVZ. At 8 PCW, PAX6 was highly expressed rostrally but less so caudally, as has been seen in the rodent, however this gradient disappeared early in corticogenesis, by 9 PCW. There was less restricted compartment-specific expression of TBR2, NEUROD and TBR1 mRNA than in the rodent, where the gradients of expression were similar to that of PAX6 prior to 9 PCW. The gradient disappeared for TBR2 by 10 PCW, and for NEUROD and TBR1 by 12 PCW. These data support recent reports that EMX2 but not PAX6 is more directly involved in arealization, highlighting that analysis of human development allows better spatio-temporal resolution than studies in rodents.

PMID 18973570


A structural MRI study of human brain development from birth to 2 years.

Knickmeyer RC, Gouttard S, Kang C, Evans D, Wilber K, Smith JK, Hamer RM, Lin W, Gerig G, Gilmore JH. J Neurosci. 2008 Nov 19;28(47):12176-82. PMID 19020011

2004

3 dimensional modelling of early human brain development using optical projection tomography

BMC Neurosci. 2004 Aug 6;5:27.


Kerwin J, Scott M, Sharpe J, Puelles L, Robson SC, Martínez-de-la-Torre M, Ferran JL, Feng G, Baldock R, Strachan T, Davidson D, Lindsay S. Source Institute of Human Genetics, University of Newcastle upon Tyne, International Centre for Life, Central Parkway, Newcastle upon Tyne, NE1 3BZ, UK. j.m.kerwin@ncl.ac.uk

Abstract

BACKGROUND: As development proceeds the human embryo attains an ever more complex three dimensional (3D) structure. Analyzing the gene expression patterns that underlie these changes and interpreting their significance depends on identifying the anatomical structures to which they map and following these patterns in developing 3D structures over time. The difficulty of this task greatly increases as more gene expression patterns are added, particularly in organs with complex 3D structures such as the brain. Optical Projection Tomography (OPT) is a new technology which has been developed for rapidly generating digital 3D models of intact specimens. We have assessed the resolution of unstained neuronal structures within a Carnegie Stage (CS)17 OPT model and tested its use as a framework onto which anatomical structures can be defined and gene expression data mapped. RESULTS: Resolution of the OPT models was assessed by comparison of digital sections with physical sections stained, either with haematoxylin and eosin (H&E) or by immunocytochemistry for GAP43 or PAX6, to identify specific anatomical features. Despite the 3D models being of unstained tissue, peripheral nervous system structures from the trigeminal ganglion (approximately 300 microm by approximately 150 microm) to the rootlets of cranial nerve XII (approximately 20 microm in diameter) were clearly identifiable, as were structures in the developing neural tube such as the zona limitans intrathalamica (core is approximately 30 microm thick). Fourteen anatomical domains have been identified and visualised within the CS17 model. Two 3D gene expression domains, known to be defined by Pax6 expression in the mouse, were clearly visible when PAX6 data from 2D sections were mapped to the CS17 model. The feasibility of applying the OPT technology to all stages from CS12 to CS23, which encompasses the major period of organogenesis for the human developing central nervous system, was successfully demonstrated. CONCLUSION: In the CS17 model considerable detail is visible within the developing nervous system at a minimum resolution of approximately 20 microm and 3D anatomical and gene expression domains can be defined and visualised successfully. The OPT models and accompanying technologies for manipulating them provide a powerful approach to visualising and analysing gene expression and morphology during early human brain development.


PMID 15298700

1997

The timing and sequence of appearance of neuromeres and their derivatives in staged human embryos

Acta Anat (Basel). 1997;158(2):83-99.

Müller F, O'Rahilly R. Author information

Abstract

Serial sections of 215 human embryos from Carnegie stages 6-17 were investigated, and 85 graphic reconstructions were prepared. It is proposed that neuromeres be defined as morphologically identifiable transverse subdivisions perpendicular to the longitudinal axis of the embryonic brain and extending onto both sides of the body. It is proposed further that primary neuromeres be redefined as the early-appearing larger divisions of the open neural folds, and secondary neuromeres as the smaller subdivisions that are found both before and after closure of the neural tube. In the light of these definitions, 6 primary neuromeres can be detected in the human brain at stage 9, and a maximum of 16 secondary neuromeres at stage 14. The relationships of the 8 rhombomeres to the associated neural crest, as well as to the pharyngeal arches and the exits of the cranial nerves, are tabulated. Rhombomere 8 (Rh. 8) is intermediate between the more rostral neuromeres and the spinal cord, and its neural relationships indicate that the four occipital somitic pairs do not impress a strictly repetitive pattern as in the spinal cord. Hence, it is suggested that Rh. 8 depends on both intrinsic and extrinsic factors. The synencephalon, parencephalon, and isthmic neuromere can be distinguished in stage 13. In stage 14, rostral and caudal portions of the parencephalon are recognizable, and the full complement of 16 neuromeres is now present. The medial ventricular eminence appears in the diencephalon (D1). A longitudinal organisation begins to be superimposed on the neuromeres, as now indicated by the appearance of the hypothalamic cell cord. This continues in stage 15, when the hypothalamic sulcus develops. That groove, however, is not continuous with the sulcus limitans. In the diencephalon, five longitudinal zones can be discerned. In stage 16, fibre tracts, such as the habenulo-interpeduncular (fasciculus retroflexus) and the tract of the posterior commissure, outline the boundaries of the synencephalon. In stage 17, the tract of the zona limitans intrathalamica (along the marginal ridge in the parencephalon) is an important landmark. This is the last stage in which all the neuromeres can be distinguished. The supramamillary recess becomes defined and is the termination of the sulcus limitans: the alar/basal distinction is inappropriate in the human forebrain. The number and identity of the neuromeres in the human brain, their precise sequence of appearance, and the stages at which they appear are here clarified for the first time. The results of various studies of domains of gene expression indicate that, although in some instances such territories follow the morphological neuromeres, in others they may cross interneuromeric boundaries. It is concluded that the precise morphological study of neuromeres in any given species is necessary for correlative investigations of gene expression. PMID 9311417

1994

Neurulation in the normal human embryo

Ciba Found Symp. 1994;181:70-82; discussion 82-9.

O'Rahilly R, Müller F. Source Institut für Anatomie und Spezielle Embryologie, Universität Freiburg, Switzerland.

Abstract

The neural groove and folds are first seen during stage 8 (about 18 postovulatory days). Two days later (stage 9) the three main divisions of the brain, which are not cerebral vesicles, can be distinguished while the neural groove is still completely open. Two days later (stage 10) the neural folds begin to fuse near the junction between brain and spinal cord, when neural crest cells are arising mainly from the neural ectoderm. The rostral (or cephalic) neuropore closes within a few hours during stage 11 (about 24 days). The closure is bidirectional; it takes place from the dorsal and terminal lips and may occur in several areas simultaneously. The two lips, however, behave differently. The caudal neuropore takes a day to close during stage 12 (about 26 days) and the level of final closure is approximately at future somitic pair 31, which corresponds to the level of sacral vertebra 2. At stage 13 (4 weeks) the neural tube is normally completely closed. Secondary neurulation, which begins at stage 12, is the differentiation of the caudal part of the neural tube from the caudal eminence (or end-bud) without the intermediate phase of a neural plate.

PMID 8005032

Neural Development Table

Neural Tube Primary Vesicles Secondary Vesicles Adult Structures
Brain Prosencephalon Telencephalon Rhinencephalon, Amygdala, Hippocampus, Neocortex, Basal Ganglia, Lateral Ventricles
Diencephalon Epithalamus, Thalamus, Hypothalamus, Subthalamus, Pituitary, Pineal, Third ventricle
Mesencephalon Mesencephalon Tectum, Cerebral peduncle, Pretectum, Cerebral aqueduct
Rhombencephalon Metencephalon Pons, Cerebellum
Myelencephalon Medulla oblongata
Spinal Cord

Neural Table Linked

Neural Tube Primary Vesicles Secondary Vesicles Adult Structures
Brain Prosencephalon Telencephalon Rhinencephalon, Amygdala, Hippocampus, Neocortex, Basal Ganglia, lateral ventricles
Diencephalon Epithalamus, Thalamus, Hypothalamus, Subthalamus, Pituitary, Pineal, third ventricle
Mesencephalon Mesencephalon Tectum, Cerebral peduncle, Pretectum, cerebral aqueduct
Rhombencephalon Metencephalon Pons, Cerebellum
Myelencephalon Medulla Oblongata
Spinal Cord
Neural Parts: neural | prosencephalon | telencephalon cerebrum | amygdala | hippocampus | basal ganglia | diencephalon | epithalamus | thalamus | hypothalamus‎ | pituitary | pineal | mesencephalon | tectum | rhombencephalon | metencephalon | pons | cerebellum | myelencephalon | medulla oblongata | spinal cord | neural vascular | ventricular | lateral ventricles | third ventricle | cerebral aqueduct | fourth ventricle | central canal | meninges | Category:Ventricular System | Category:Neural
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