Talk:Neural Crest Development

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Cite this page: Hill, M.A. 2017 Embryology Neural Crest Development. Retrieved April 28, 2017, from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Neural_Crest_Development

Neural Crest Origin
System Cell Type
Peripheral Nervous System
(PNS)
Neurons - sensory ganglia, sympathetic and parasympathetic ganglia, enteric nervous system, and plexuses

Neuroglial cells

Schwann cells

Endocrine Adrenal medulla
Calcitonin-secreting cells
Carotid body type I cells
Integumentary Epidermal pigment cells
Facial cartilage and bone Facial and anterior ventral skull cartilage and bones
Sensory Inner ear, corneal endothelium and stroma
Connective tissue Tooth papillae

Dermis?, smooth muscle, and adipose tissue of skin of head and neck

Connective tissue of salivary, lachrymal, thymus, thyroid, and pituitary glands

Connective tissue and smooth muscle in arteries of aortic arch origin

Links: Neural Crest Development | Category:Neural Crest | Neural Crest collapsible table
Neural Crest Structures
System Cell Type
Peripheral Nervous System (PNS) Neurons, including sensory ganglia, sympathetic and parasympathetic ganglia, and plexuses

Neuroglial cells

Schwann cells

Endocrine Adrenal medulla

Calcitonin-secreting cells

Carotid body type I cells

Pigment cells Epidermal pigment cells
Facial cartilage and bone Facial and anterior ventral skull cartilage and bones
Connective tissue Corneal endothelium and stroma

Tooth papillae

Dermis?, smooth muscle, and adipose tissue of skin of head and neck

Connective tissue of salivary, lachrymal, thymus, thyroid, and pituitary glands

Connective tissue and smooth muscle in arteries of aortic arch origin

10 Most Recent Papers

Note - This sub-heading shows an automated computer PubMed search using the listed sub-heading term. References appear in this list based upon the date of the actual page viewing. Therefore the list of references do not reflect any editorial selection of material based on content or relevance. In comparison, references listed on the content page and discussion page (under the publication year sub-headings) do include editorial selection based upon relevance and availability. (More? Pubmed Most Recent)


Neural Crest Development

Jiewen Dai, Jiawen Si, Ningjuan Ouyang, Jianfei Zhang, Dandan Wu, Xudong Wang, Guofang Shen Dental and periodontal phenotypes of Dlx2 overexpression in mice. Mol Med Rep: 2017; PubMed 28447749

Stefanie A Doppler, Catarina Carvalho, Harald Lahm, Marcus-André Deutsch, Martina Dreßen, Nazan Puluca, Rüdiger Lange, Markus Krane Cardiac fibroblasts: more than mechanical support. J Thorac Dis: 2017, 9(Suppl 1);S36-S51 PubMed 28446967

Dorota Szumska, Milena Cioroch, Angela Keeling, Annik Prat, Nabil G Seidah, Shoumo Bhattacharya Pcsk5 is required in the early cranio-cardiac mesoderm for heart development. BMC Dev. Biol.: 2017, 17(1);6 PubMed 28446132

Eisuke Kawano, Taku Toriumi, Shinya Iguchi, Daigo Suzuki, Shuichi Sato, Masaki Honda Induction of neural crest cells from human dental pulp-derived induced pluripotent stem cells. Biomed. Res.: 2017, 38(2);135-147 PubMed 28442664

Jie Chen, Xiaoyu Liu, Xiaohua Yao, Fei Gao, Baolong Bao Dorsal fin development in flounder, Paralichthys olivaceus: Bud formation and its cellular origin. Gene Expr. Patterns: 2017; PubMed 28442438


2016

Exclusion of Dlx5/6 expression from the distal-most mandibular arches enables BMP-mediated specification of the distal cap

Proc Natl Acad Sci U S A. 2016 Jul 5;113(27):7563-8. doi: 10.1073/pnas.1603930113. Epub 2016 Jun 22.

Vincentz JW1, Casasnovas JJ1, Barnes RM2, Que J3, Clouthier DE4, Wang J5, Firulli AB6.

Abstract

Cranial neural crest cells (crNCCs) migrate from the neural tube to the pharyngeal arches (PAs) of the developing embryo and, subsequently, differentiate into bone and connective tissue to form the mandible. Within the PAs, crNCCs respond to local signaling cues to partition into the proximo-distally oriented subdomains that convey positional information to these developing tissues. Here, we show that the distal-most of these subdomains, the distal cap, is marked by expression of the transcription factor Hand1 (H1) and gives rise to the ectomesenchymal derivatives of the lower incisors. We uncover a H1 enhancer sufficient to drive reporter gene expression within the crNCCs of the distal cap. We show that bone morphogenic protein (BMP) signaling and the transcription factor HAND2 (H2) synergistically regulate H1 distal cap expression. Furthermore, the homeodomain proteins distal-less homeobox 5 (DLX5) and DLX6 reciprocally inhibit BMP/H2-mediated H1 enhancer regulation. These findings provide insights into how multiple signaling pathways direct transcriptional outcomes that pattern the developing jaw. KEYWORDS: Bmp; DLX; HAND1; cranial neural crest cells; development PMID 27335460

Neuronal differentiation in the developing human spinal ganglia

Anat Rec (Hoboken). 2016 May 25. doi: 10.1002/ar.23376. [Epub ahead of print]

Vukojevic K1, Filipovic N1, Tica Sedlar I1,2, Restovic I3, Bocina I4, Pintaric I1, Saraga-Babic M1.

Abstract

The spatiotemporal developmental pattern of the neural crest cells differentiation towards the first appearance of the neuronal subtypes was investigated in developing human spinal ganglia between the 5th -10th developmental week using immunohistochemistry and immunofluorescence methods. First NF200 (neurofilament-200, likely-myelinated mechanoreceptors) and isolectin-B4 positive neurons (likely-unmyelinated nociceptors) appeared already in the 5/6th developmental week and their number subsequently increased during progression of development. Proportion of NF200 positive cells was higher in the ventral parts of the spinal ganglia than in the dorsal parts, particularly during the 5/6th and 9/10th developmental weeks (Mann-Whitney, p=0.040 and p=0.003). NF200 and IB4 co-localized during the whole investigated period. Calcitonin gene-related peptide (CGRP, nociceptive responses), vanilloid-receptor-1 (VR1, polymodal nociceptors) and calretinin (calcium signalling) cell immunoreactivity first appeared in the 6th and 8th week, respectively, especially in the dorsal parts of the spinal ganglia. VR1 and CGRP co-localized with NF00 during the whole investigated period. Our results indicate the high potential of early differentiated neuronal cells, which slightly decreased with progression of spinal ganglia differentiation. On the contrary, the number of neuronal subtypes displayed increasing differentiation at later developmental stage. The great diversity of phenotypic expression found in the spinal ganglia neurons is the result of a wide variety of influences, occurring at different stages of development in a large potential repertory of these neurons. Understanding the pathway of neural differentiation in the human spinal ganglia could be important for the studies dealing with process of regeneration of damaged spinal nerves or during repair of pathological changes within affected ganglia. This article is protected by copyright. All rights reserved. © 2016 Wiley Periodicals, Inc. KEYWORDS: CGRP; IB4; NF200; VR1; human embryo; spinal ganglia

PMID 27225905

The Hippo pathway member YAP enhances human neural crest cell fate and migration

Sci Rep. 2016 Mar 16;6:23208. doi: 10.1038/srep23208.

Hindley CJ1, Condurat AL1,2, Menon V1,2, Thomas R1,2, Azmitia LM1, Davis JA1, Pruszak J1,3.

Abstract

The Hippo/YAP pathway serves as a major integrator of cell surface-mediated signals and regulates key processes during development and tumorigenesis. The neural crest is an embryonic tissue known to respond to multiple environmental cues in order to acquire appropriate cell fate and migration properties. Using multiple in vitro models of human neural development (pluripotent stem cell-derived neural stem cells; LUHMES, NTERA2 and SH-SY5Y cell lines), we investigated the role of Hippo/YAP signaling in neural differentiation and neural crest development. We report that the activity of YAP promotes an early neural crest phenotype and migration, and provide the first evidence for an interaction between Hippo/YAP and retinoic acid signaling in this system. PMID 26980066


2015

VEGF signals induce trailblazer cell identity that drives neural crest migration

Dev Biol. 2015 Nov 1;407(1):12-25. doi: 10.1016/j.ydbio.2015.08.011. Epub 2015 Aug 13.

McLennan R1, Schumacher LJ2, Morrison JA1, Teddy JM1, Ridenour DA1, Box AC1, Semerad CL1, Li H1, McDowell W1, Kay D3, Maini PK4, Baker RE4, Kulesa PM5.

Abstract Embryonic neural crest cells travel in discrete streams to precise locations throughout the head and body. We previously showed that cranial neural crest cells respond chemotactically to vascular endothelial growth factor (VEGF) and that cells within the migratory front have distinct behaviors and gene expression. We proposed a cell-induced gradient model in which lead neural crest cells read out directional information from a chemoattractant profile and instruct trailers to follow. In this study, we show that migrating chick neural crest cells do not display distinct lead and trailer gene expression profiles in culture. However, exposure to VEGF in vitro results in the upregulation of a small subset of genes associated with an in vivo lead cell signature. Timed addition and removal of VEGF in culture reveals the changes in neural crest cell gene expression are rapid. A computational model incorporating an integrate-and-switch mechanism between cellular phenotypes predicts migration efficiency is influenced by the timescale of cell behavior switching. To test the model hypothesis that neural crest cellular phenotypes respond to changes in the VEGF chemoattractant profile, we presented ectopic sources of VEGF to the trailer neural crest cell subpopulation and show diverted cell trajectories and stream alterations consistent with model predictions. Gene profiling of trailer cells that diverted and encountered VEGF revealed upregulation of a subset of 'lead' genes. Injection of neuropilin1 (Np1)-Fc into the trailer subpopulation or electroporation of VEGF morpholino to reduce VEGF signaling failed to alter trailer neural crest cell trajectories, suggesting trailers do not require VEGF to maintain coordinated migration. These results indicate that VEGF is one of the signals that establishes lead cell identity and its chemoattractant profile is critical to neural crest cell migration. Copyright © 2015 Elsevier Inc. All rights reserved. KEYWORDS: Cell migration; Chick; Computational modeling; Embryonic microenvironment; Gene expression; Molecular profile; Neural crest; Trailblazers PMID 26278036

Meis2 is essential for cranial and cardiac neural crest development

BMC Dev Biol. 2015 Nov 6;15(1):40. doi: 10.1186/s12861-015-0093-6.

Machon O1, Masek J2, Machonova O3, Krauss S4, Kozmik Z5.

Abstract

BACKGROUND: TALE-class homeodomain transcription factors Meis and Pbx play important roles in formation of the embryonic brain, eye, heart, cartilage or hematopoiesis. Loss-of-function studies of Pbx1, 2 and 3 and Meis1 documented specific functions in embryogenesis, however, functional studies of Meis2 in mouse are still missing. We have generated a conditional allele of Meis2 in mice and shown that systemic inactivation of the Meis2 gene results in lethality by the embryonic day 14 that is accompanied with hemorrhaging. RESULTS: We show that neural crest cells express Meis2 and Meis2-defficient embryos display defects in tissues that are derived from the neural crest, such as an abnormal heart outflow tract with the persistent truncus arteriosus and abnormal cranial nerves. The importance of Meis2 for neural crest cells is further confirmed by means of conditional inactivation of Meis2 using crest-specific AP2α-IRES-Cre mouse. Conditional mutants display perturbed development of the craniofacial skeleton with severe anomalies in cranial bones and cartilages, heart and cranial nerve abnormalities. CONCLUSIONS: Meis2-null mice are embryonic lethal. Our results reveal a critical role of Meis2 during cranial and cardiac neural crest cells development in mouse.

PMID 26545946 http://bmcdevbiol.biomedcentral.com/articles/10.1186/s12861-015-0093-6

Pentimento: Neural Crest and the origin of mesectoderm

Dev Biol. 2015 May 1;401(1):37-61. doi: 10.1016/j.ydbio.2014.12.035. Epub 2015 Jan 15.

Weston JA1, Thiery JP2.

Abstract

The Neural Crest, a transient epithelium in vertebrate embryos, is the source of putative stem cells known to give rise to neuronal, glial and endocrine components of the peripheral (sensory, autonomic and enteric) nervous system (PNS) and pigment cells in the skin. The Neural Crest is also widely believed to be the source of mesectodermal derivatives (skeletogenic, odontogenic, connective tissue and smooth muscle mesenchyme) in the vertebrate head [see (Bronner and LeDouarin, 2012; Le Douarin, 2012; Le Douarin and Kalcheim, 1999); see also (Hörstadius, 1950; Weston, 1970)]. This conventional understanding of the broad developmental potential of the Neural Crest has been challenged over the past few years (Breau et al., 2008; Lee et al., 2013a, 2013b; Weston et al., 2004), based on recognition that the definition of the embryonic epithelia that comprise the Neural Crest may be imprecise. Indeed, the definition of the embryonic tissues understood to constitute the Neural Crest has changed considerably since it was first described by Wilhelm His 150 years ago (His, 1868). Today, the operational definition of the Neural Crest is inconsistent and functionally ambiguous. We believe that more precise definitions of the embryonic tissues involved in Neural Crest development would be useful to understand (1) the range of cellular phenotypes that actually segregate from it, (2) when this lineage diversification occurs, and (3) how diversification is regulated. In this idiosyncratic review, we aim to explain our concerns with the current definitions in this field, and in the chiastic words of Samuel Johnson (1781), "… make new things familiar and familiar things new".(1) Then, we will try to distinguish the developmental events crucial to the regulation of Neural Crest development at both cranial and trunk axial levels of vertebrate embryos, and address some of the implicit assumptions that underlie the conventional interpretation of experimental results on the origin and fates of Neural Crest-derived cells. We hope our discussion will resolve some ambiguities regarding both the range of derivatives in the Neural Crest lineage and the conventional understanding that cranial mesectodermal derivatives share a common Neural Crest-derived lineage precursor with components of the PNS. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved. KEYWORDS: Cell fate determination; EMT; Mesectoderm; Metablast; Neural Crest; Neural fold

PMID 25598524

http://www.sciencedirect.com/science/article/pii/S0012160615000056

NEURODEVELOPMENT. Shared regulatory programs suggest retention of blastula-stage potential in neural crest cells

Science. 2015 Jun 19;348(6241):1332-5. doi: 10.1126/science.aaa3655. Epub 2015 Apr 30.

Buitrago-Delgado E1, Nordin K1, Rao A1, Geary L1, LaBonne C2.

Abstract

Neural crest cells, which are specific to vertebrates, arise in the ectoderm but can generate cell types that are typically categorized as mesodermal. This broad developmental potential persists past the time when most ectoderm-derived cells become lineage-restricted. The ability of neural crest to contribute mesodermal derivatives to the bauplan has raised questions about how this apparent gain in potential is achieved. Here, we describe shared molecular underpinnings of potency in neural crest and blastula cells. We show that in Xenopus, key neural crest regulatory factors are also expressed in blastula animal pole cells and promote pluripotency in both cell types. We suggest that neural crest cells may have evolved as a consequence of a subset of blastula cells retaining activity of the regulatory network underlying pluripotency. Copyright © 2015, American Association for the Advancement of Science. Comment in DEVELOPMENTAL BIOLOGY. It's about time for neural crest. [Science. 2015]

PMID 25931449

Evolution of vertebrates as viewed from the crest

Nature. 2015 Apr 23;520(7548):474-82. doi: 10.1038/nature14436.

Green SA1, Simoes-Costa M1, Bronner ME1.

Abstract

The origin of vertebrates was accompanied by the advent of a novel cell type: the neural crest. Emerging from the central nervous system, these cells migrate to diverse locations and differentiate into numerous derivatives. By coupling morphological and gene regulatory information from vertebrates and other chordates, we describe how addition of the neural-crest-specification program may have enabled cells at the neural plate border to acquire multipotency and migratory ability. Analysis of the topology of the neural crest gene regulatory network can serve as a useful template for understanding vertebrate evolution, including elaboration of neural crest derivatives.

PMID 25903629

http://www.nature.com/nature/journal/v520/n7548/full/nature14436.html

The neural crest: a versatile organ system

Birth Defects Res C Embryo Today. 2014 Sep;102(3):275-98. doi: 10.1002/bdrc.21081. Epub 2014 Sep 16.

Zhang D1, Ighaniyan S, Stathopoulos L, Rollo B, Landman K, Hutson J, Newgreen D.

Abstract

The neural crest is the name given to the strip of cells at the junction between neural and epidermal ectoderm in neurula-stage vertebrate embryos, which is later brought to the dorsal neural tube as the neural folds elevate. The neural crest is a heterogeneous and multipotent progenitor cell population whose cells undergo EMT then extensively and accurately migrate throughout the embryo. Neural crest cells contribute to nearly every organ system in the body, with derivatives of neuronal, glial, neuroendocrine, pigment, and also mesodermal lineages. This breadth of developmental capacity has led to the neural crest being termed the fourth germ layer. The neural crest has occupied a prominent place in developmental biology, due to its exaggerated migratory morphogenesis and its remarkably wide developmental potential. As such, neural crest cells have become an attractive model for developmental biologists for studying these processes. Problems in neural crest development cause a number of human syndromes and birth defects known collectively as neurocristopathies; these include Treacher Collins syndrome, Hirschsprung disease, and 22q11.2 deletion syndromes. Tumors in the neural crest lineage are also of clinical importance, including the aggressive melanoma and neuroblastoma types. These clinical aspects have drawn attention to the selection or creation of neural crest progenitor cells, particularly of human origin, for studying pathologies of the neural crest at the cellular level, and also for possible cell therapeutics. The versatility of the neural crest lends itself to interlinked research, spanning basic developmental biology, birth defect research, oncology, and stem/progenitor cell biology and therapy. © 2014 Wiley Periodicals, Inc. KEYWORDS: cell migration; neural crest; neurocristopathy; progenitor cell

PMID 25227568

2014

Neural crest-derived mesenchymal cells require wnt signaling for their development and drive invagination of the telencephalic midline

PLoS One. 2014 Feb 6;9(2):e86025. doi: 10.1371/journal.pone.0086025. eCollection 2014.

Choe Y1, Zarbalis KS2, Pleasure SJ3. Author information

Abstract Embryonic neural crest cells contribute to the development of the craniofacial mesenchyme, forebrain meninges and perivascular cells. In this study, we investigated the function of ß-catenin signaling in neural crest cells abutting the dorsal forebrain during development. In the absence of ß-catenin signaling, neural crest cells failed to expand in the interhemispheric region and produced ectopic smooth muscle cells instead of generating dermal and calvarial mesenchyme. In contrast, constitutive expression of stabilized ß-catenin in neural crest cells increased the number of mesenchymal lineage precursors suggesting that ß-catenin signaling is necessary for the expansion of neural crest-derived mesenchymal cells. Interestingly, the loss of neural crest-derived mesenchymal stem cells (MSCs) leads to failure of telencephalic midline invagination and causes ventricular system defects. This study shows that ß-catenin signaling is required for the switch of neural crest cells to MSCs and mediates the expansion of MSCs to drive the formation of mesenchymal structures of the head. Furthermore, loss of these structures causes striking defects in forebrain morphogenesis.


PMID 24516524

2013

Signals and switches in Mammalian neural crest cell differentiation

Cold Spring Harb Perspect Biol. 2013 Feb 1;5(2). pii: a008326. doi: 10.1101/cshperspect.a008326.

Bhatt S, Diaz R, Trainor PA. Source Stowers Institute for Medical Research, Kansas City, Missouri 64110.

Abstract

Neural crest cells (NCCs) comprise a multipotent, migratory cell population that generates a diverse array of cell and tissue types during vertebrate development. These include cartilage and bone, tendons, and connective tissue, as well as neurons, glia, melanocytes, and endocrine and adipose cells; this remarkable lineage potential persists into adult life. Taken together with a limited capacity for self-renewal, neural crest cells bear the hallmarks of stem and progenitor cells and are considered to be synonymous with vertebrate evolution. The neural crest has provided a system for exploring the mechanisms that govern developmental processes such as morphogenetic induction, cell migration, and fate determination. Today, much of the focus on neural crest cells revolves around their stem cell-like characteristics and potential for use in regenerative medicine. A thorough understanding of the signals and switches that govern mammalian neural crest patterning is central to potential therapeutic application of these cells and better appreciation of the role that neural crest cells play in vertebrate evolution, development, and disease.

PMID 23378583

http://cshperspectives.cshlp.org/content/5/2/a008326.abstract

2012

Annexin a6 modulates chick cranial neural crest cell emigration

PLoS One. 2012;7(9):e44903. doi: 10.1371/journal.pone.0044903. Epub 2012 Sep 11.

Wu CY, Taneyhill LA. Source Department of Animal and Avian Sciences, University of Maryland, College Park, Maryland, United States of America.

Abstract

The vertebrate neural crest is a population of migratory cells that originates in the dorsal aspect of the embryonic neural tube. These cells undergo an epithelial-to-mesenchymal transition (EMT), delaminate from the neural tube and migrate extensively to generate an array of differentiated cell types. Elucidating the gene regulatory networks involved in neural crest cell induction, migration and differentiation are thus crucial to understanding vertebrate development. To this end, we have identified Annexin A6 as an important regulator of chick midbrain neural crest cell emigration. Annexin proteins comprise a family of calcium-dependent, membrane-binding molecules that mediate a variety of cellular and physiological processes including cell adhesion, migration and invasion. Our data indicate that Annexin A6 is expressed in the proper spatio-temporal pattern in the chick midbrain to play a potential role in neural crest cell ontogeny. To investigate Annexin A6 function, we have depleted or overexpressed Annexin A6 in the developing midbrain neural crest cell population. Our results show that knock-down or overexpression of Annexin A6 reduces or expands the migratory neural crest cell domain, respectively. Importantly, this phenotype is not due to any change in cell proliferation or cell death but can be correlated with changes in the size of the premigratory neural crest cell population and with markers associated with EMT. Taken together, our data indicate that Annexin A6 plays a pivotal role in modulating the formation of cranial migratory neural crest cells during vertebrate development.

PMID 22984583

An essential role of variant histone h3.3 for ectomesenchyme potential of the cranial neural crest

PLoS Genet. 2012 Sep;8(9):e1002938. doi: 10.1371/journal.pgen.1002938. Epub 2012 Sep 20.

Cox SG, Kim H, Garnett AT, Medeiros DM, An W, Crump JG. Source Department of Cell and Neurobiology, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of Southern California Keck School of Medicine, Los Angeles, California, United States of America.

Abstract

The neural crest (NC) is a vertebrate-specific cell population that exhibits remarkable multipotency. Although derived from the neural plate border (NPB) ectoderm, cranial NC (CNC) cells contribute not only to the peripheral nervous system but also to the ectomesenchymal precursors of the head skeleton. To date, the developmental basis for such broad potential has remained elusive. Here, we show that the replacement histone H3.3 is essential during early CNC development for these cells to generate ectomesenchyme and head pigment precursors. In a forward genetic screen in zebrafish, we identified a dominant D123N mutation in h3f3a, one of five zebrafish variant histone H3.3 genes, that eliminates the CNC-derived head skeleton and a subset of pigment cells yet leaves other CNC derivatives and trunk NC intact. Analyses of nucleosome assembly indicate that mutant D123N H3.3 interferes with H3.3 nucleosomal incorporation by forming aberrant H3 homodimers. Consistent with CNC defects arising from insufficient H3.3 incorporation into chromatin, supplying exogenous wild-type H3.3 rescues head skeletal development in mutants. Surprisingly, embryo-wide expression of dominant mutant H3.3 had little effect on embryonic development outside CNC, indicating an unexpectedly specific sensitivity of CNC to defects in H3.3 incorporation. Whereas previous studies had implicated H3.3 in large-scale histone replacement events that generate totipotency during germ line development, our work has revealed an additional role of H3.3 in the broad potential of the ectoderm-derived CNC, including the ability to make the mesoderm-like ectomesenchymal precursors of the head skeleton.

PMID 23028350

http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1002938

Pax7 lineage contributions to the Mammalian neural crest

PLoS One. 2012;7(7):e41089. Epub 2012 Jul 27.

Murdoch B, Delconte C, García-Castro MI. Source Biology Department, Eastern Connecticut State University, Willimantic, Connecticut, United States of America.

Abstract

BACKGROUND: Neural crest cells are vertebrate-specific multipotent cells that contribute to a variety of tissues including the peripheral nervous system, melanocytes, and craniofacial bones and cartilage. Abnormal development of the neural crest is associated with several human maladies including cleft/lip palate, aggressive cancers such as melanoma and neuroblastoma, and rare syndromes, like Waardenburg syndrome, a complex disorder involving hearing loss and pigment defects. We previously identified the transcription factor Pax7 as an early marker, and required component for neural crest development in chick embryos. In mammals, Pax7 is also thought to play a role in neural crest development, yet the precise contribution of Pax7 progenitors to the neural crest lineage has not been determined. METHODOLOGY/PRINCIPAL FINDINGS: Here we use Cre/loxP technology in double transgenic mice to fate map the Pax7 lineage in neural crest derivates. We find that Pax7 descendants contribute to multiple tissues including the cranial, cardiac and trunk neural crest, which in the cranial cartilage form a distinct regional pattern. The Pax7 lineage, like the Pax3 lineage, is additionally detected in some non-neural crest tissues, including a subset of the epithelial cells in specific organs. CONCLUSIONS/SIGNIFICANCE: These results demonstrate a previously unappreciated widespread distribution of Pax7 descendants within and beyond the neural crest. They shed light regarding the regionally distinct phenotypes observed in Pax3 and Pax7 mutants, and provide a unique perspective into the potential roles of Pax7 during disease and development.

PMID 22848431

2011

Dual embryonic origin of the mammalian otic vesicle forming the inner ear

Development. 2011 Dec;138(24):5403-14. doi: 10.1242/dev.069849.

Freyer L1, Aggarwal V, Morrow BE.

Abstract

The inner ear and cochleovestibular ganglion (CVG) derive from a specialized region of head ectoderm termed the otic placode. During embryogenesis, the otic placode invaginates into the head to form the otic vesicle (OV), the primordium of the inner ear and CVG. Non-autonomous cell signaling from the hindbrain to the OV is required for inner ear morphogenesis and neurogenesis. In this study, we show that neuroepithelial cells (NECs), including neural crest cells (NCCs), can contribute directly to the OV from the neural tube. Using Wnt1-Cre, Pax3(Cre/+) and Hoxb1(Cre/+) mice to label and fate map cranial NEC lineages, we have demonstrated that cells from the neural tube incorporate into the otic epithelium after otic placode induction has occurred. Pax3(Cre/+) labeled a more extensive population of NEC derivatives in the OV than did Wnt1-Cre. NEC derivatives constitute a significant population of the OV and, moreover, are regionalized specifically to proneurosensory domains. Descendents of Pax3(Cre/+) and Wnt1-Cre labeled cells are localized within sensory epithelia of the saccule, utricle and cochlea throughout development and into adulthood, where they differentiate into hair cells and supporting cells. Some NEC derivatives give rise to neuroblasts in the OV and CVG, in addition to their known contribution to glial cells. This study defines a dual cellular origin of the inner ear from sensory placode ectoderm and NECs, and changes the current paradigm of inner ear neurosensory development.

PMID 22110056

Migration and maturation pattern of fetal enteric ganglia: a study of 16 cases

Indian J Pathol Microbiol. 2011 Apr-Jun;54(2):269-72.

Bandyopadhyay R, Chatterjee U, Bandyopadhyay SK, Basu AK. Source Department of Pathology, Burdwan Medical College, Kolkata, India. drranjanapatho@gmail.com

Abstract

AIMS: To study the migration and developmental pattern of ganglion cells in fetuses aged 9-21 weeks, and to document whether the migration was occurring circumferentially equally in the entire axis or if there were discrepancies in different portions at the same level. SETTINGS AND DESIGN: The hypothesis regarding the pathogenesis of Hirschsprung's disease mainly revolves around two schools. One is the single gradient migration of ganglia and the other is a dual gradient migration theory. Understanding the embryological development of enteric ganglia is necessary to study the pathogenesis of intestinal innervation disorders. MATERIALS AND METHODS: We studied the development of intestinal ganglia in fetuses aged 9-21 weeks. Serial longitudinal sections from the colon were studied, the first one including the squamo-columnar junction, for the presence and the nature of ganglion cells with Hematoxylin and Eosin, and neurone-specific enolase immunostaining. Transverse sections from proximal gut were studied in a similar fashion. Thus, we evaluated the migration pattern as well as the nature of ganglia in the fetuses. We also measured the length of distal aganglionic segment in these growing fetuses. RESULTS: We noted that ganglion cells appear first in the myenteric plexus followed by deep and superficial submucous plexus. We also found evidences in favor of dual migration theory, and the distal aganglionic segment varies around the circumference of the rectal wall. CONCLUSIONS: We got evidences in support of a dual migration pattern of intestinal ganglion cells. The level of distal aganglionic segments when measured from squamo-columnar junction varied with the age of gestation and the length was incongruous. The description of distal aganglionic segment may help surgeons while taking biopsies or during operative procedures.

PMID 21623072

Early emergence of neural activity in the developing mouse enteric nervous system

J Neurosci. 2011 Oct 26;31(43):15352-61.

Hao MM, Boesmans W, Van den Abbeel V, Jennings EA, Bornstein JC, Young HM, Vanden Berghe P. Source Department of Anatomy and Cell Biology, University of Melbourne, Parkville, Victoria 3010, Australia. Abstract Neurons of the enteric nervous system (ENS) arise from neural crest cells that migrate into and along the developing gastrointestinal tract. A subpopulation of these neural-crest derived cells express pan-neuronal markers early in development, shortly after they first enter the gut. However, it is unknown whether these early enteric "neurons" are electrically active. In this study we used live Ca(2+) imaging to examine the activity of enteric neurons from mice at embryonic day 11.5 (E11.5), E12.5, E15.5, and E18.5 that were dissociated and cultured overnight. PGP9.5-immunoreactive neurons from E11.5 gut cultures responded to electrical field stimulation with fast [Ca(2+)](i) transients that were sensitive to TTX and ω-conotoxin GVIA, suggesting roles for voltage-gated Na(+) channels and N-type voltage-gated Ca(2+) channels. E11.5 neurons were also responsive to the nicotinic cholinergic agonist, dimethylphenylpiperazinium, and to ATP. In addition, spontaneous [Ca(2+)](i) transients were present. Similar responses were observed in neurons from older embryonic gut. Whole-cell patch-clamp recordings performed on E12.5 enteric neurons after 2-10 h in culture revealed that these neurons fired both spontaneous and evoked action potentials. Together, our results show that enteric neurons exhibit mature forms of activity at early stages of ENS development. This is the first investigation to directly examine the presence of neural activity during enteric neuron development. Along with the spinal cord and hindbrain, the ENS appears to be one of the earliest parts of the nervous system to exhibit electrical activity.

PMID 22031881

Novel migrating mouse neural crest cell assay system utilizing P0-Cre/EGFP fluorescent time-lapse imaging

BMC Dev Biol. 2011 Nov 9;11:68.

Kawakami M, Umeda M, Nakagata N, Takeo T, Yamamura K. Source Division of Developmental Genetics, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto-City, Kumamoto, 860-0811, Japan. mkawa@gpo.kumamoto-u.ac.jp

Abstract

BACKGROUND: Neural crest cells (NCCs) are embryonic, multipotent stem cells. Their long-range and precision-guided migration is one of their most striking characteristics. We previously reported that P0-Cre/CAG-CAT-lacZ double-transgenic mice showed significant lacZ expression in tissues derived from NCCs. RESULTS: In this study, by embedding a P0-Cre/CAG-CAT-EGFP embryo at E9.5 in collagen gel inside a culture glass slide, we were able to keep the embryo developing ex vivo for more than 24 hours; this development was with enough NCC fluorescent signal intensity to enable single-cell resolution analysis, with the accompanying NCC migration potential intact and with the appropriate NCC response to the extracellular signal maintained. By implantation of beads with absorbed platelet-derived growth factor-AA (PDGF-AA), we demonstrated that PDGF-AA acts as an NCC-attractant in embryos.We also performed assays with NCCs isolated from P0-Cre/CAG-CAT-EGFP embryos on culture plates. The neuromediator 5-hydroxytryptamine (5-HT) has been known to regulate NCC migration. We newly demonstrated that dopamine, in addition to 5-HT, stimulated NCC migration in vitro. Two NCC populations, with different axial levels of origins, showed unique distribution patterns regarding migration velocity and different dose-response patterns to both 5-HT and dopamine. CONCLUSIONS: Although avian species predominated over the other species in the NCC study, our novel system should enable us to use mice to assay many different aspects of NCCs in embryos or on culture plates, such as migration, division, differentiation, and apoptosis.

PMID 22070366

http://www.biomedcentral.com/1471-213X/11/68

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3224755


This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Differential contribution of Neurog1 and Neurog2 on the formation of cranial ganglia along the anterior-posterior axis

Abstract The neural crest (NC) and placode are transient neurogenic cell populations that give rise to cranial ganglia of the vertebrate head. The formation of the anterior NC- and placode-derived ganglia has been shown to depend on the single activity of either Neurog1 or Neurog2. The requirement of the more posterior cranial ganglia on Neurog1 and Neurog2 is unknown. Here we show that the formation of the NC-derived parasympathetic otic ganglia, and placode-derived visceral sensory petrosal and nodose ganglia are dependent on the redundant activities of Neurog1 and Neurog2. Tamoxifen-inducible Cre lineage labeling of Neurog1 and Neurog2 show a dynamic spatiotemporal expression profile in both NC and epibranchial placode that correlates with the phenotypes of the Neurog-mutant embryos. Our data, together with previous studies, suggest that the formation of cranial ganglia along the anterior-posterior axis is dependent on the dynamic spatiotemporal activities of Neurog1 and/or Neurog2 in both NC and epibranchial placode. Developmental Dynamics, 2011. © 2011 Wiley Periodicals, Inc.

Expression of PROKR1 and PROKR2 in Human Enteric Neural Precursor Cells and Identification of Sequence Variants Suggest a Role in HSCR

PLoS One. 2011;6(8):e23475. Epub 2011 Aug 12.PLoS One. 2011;6(8):e23475. Epub 2011 Aug 12.

Ruiz-Ferrer M, Torroglosa A, Núñez-Torres R, de Agustín JC, Antiñolo G, Borrego S. Source Unidad de Gestión Clínica de Genética, Reproducción y Medicina Fetal, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.

Abstract

BACKGROUND: The enteric nervous system (ENS) is entirely derived from neural crest and its normal development is regulated by specific molecular pathways. Failure in complete ENS formation results in aganglionic gut conditions such as Hirschsprung's disease (HSCR). Recently, PROKR1 expression has been demonstrated in mouse enteric neural crest derived cells and Prok-1 was shown to work coordinately with GDNF in the development of the ENS.

PRINCIPAL FINDINGS: In the present report, ENS progenitors were isolated and characterized from the ganglionic gut from children diagnosed with and without HSCR, and the expression of prokineticin receptors was examined. Immunocytochemical analysis of neurosphere-forming cells demonstrated that both PROKR1 and PROKR2 were present in human enteric neural crest cells. In addition, we also performed a mutational analysis of PROKR1, PROKR2, PROK1 and PROK2 genes in a cohort of HSCR patients, evaluating them for the first time as susceptibility genes for the disease. Several missense variants were detected, most of them affecting highly conserved amino acid residues of the protein and located in functional domains of both receptors, which suggests a possible deleterious effect in their biological function.

CONCLUSIONS: Our results suggest that not only PROKR1, but also PROKR2 might mediate a complementary signalling to the RET/GFRα1/GDNF pathway supporting proliferation/survival and differentiation of precursor cells during ENS development. These findings, together with the detection of sequence variants in PROKR1, PROK1 and PROKR2 genes associated to HSCR and, in some cases in combination with RET or GDNF mutations, provide the first evidence to consider them as susceptibility genes for HSCR.

PMID 21858136 http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0023475

A Src-Tks5 Pathway Is Required for Neural Crest Cell Migration during Embryonic Development

PLoS One. 2011;6(7):e22499. Epub 2011 Jul 25.

Murphy DA, Diaz B, Bromann PA, Tsai JH, Kawakami Y, Maurer J, Stewart RA, Izpisúa-Belmonte JC, Courtneidge SA. Source Sanford-Burnham Medical Research Institute, La Jolla, California, United States of America.

Abstract

In the adult organism, cell migration is required for physiological processes such as angiogenesis and immune surveillance, as well as pathological events such as tumor metastasis. The adaptor protein and Src substrate Tks5 is necessary for cancer cell migration through extracellular matrix in vitro and tumorigenicity in vivo. However, a role for Tks5 during embryonic development, where cell migration is essential, has not been examined. We used morpholinos to reduce Tks5 expression in zebrafish embryos, and observed developmental defects, most prominently in neural crest-derived tissues such as craniofacial structures and pigmentation. The Tks5 morphant phenotype was rescued by expression of mammalian Tks5, but not by a variant of Tks5 in which the Src phosphorylation sites have been mutated. We further evaluated the role of Tks5 in neural crest cells and neural crest-derived tissues and found that loss of Tks5 impaired their ventral migration. Inhibition of Src family kinases also led to abnormal ventral patterning of neural crest cells and their derivatives. We confirmed that these effects were likely to be cell autonomous by shRNA-mediated knockdown of Tks5 in a murine neural crest stem cell line. Tks5 was required for neural crest cell migration in vitro, and both Src and Tks5 were required for the formation of actin-rich structures with similarity to podosomes. Additionally, we observed that neural crest cells formed Src-Tks5-dependent cell protrusions in 3-D culture conditions and in vivo. These results reveal an important and novel role for the Src-Tks5 pathway in neural crest cell migration during embryonic development. Furthermore, our data suggests that this pathway regulates neural crest cell migration through the generation of actin-rich pro-migratory structures, implying that similar mechanisms are used to control cell migration during embryogenesis and cancer metastasis.

PMID 21799874

Dbx1-expressing cells are necessary for the survival of the mammalian anterior neural and craniofacial structures

PLoS One. 2011 Apr 28;6(4):e19367.

Causeret F, Ensini M, Teissier A, Kessaris N, Richardson WD, Lucas de Couville T, Pierani A. Source CNRS UMR 7592, Institut Jacques Monod, Univ Paris Diderot, Sorbonne Paris Cité, Paris, France.

Abstract

Development of the vertebrate forebrain and craniofacial structures are intimately linked processes, the coordinated growth of these tissues being required to ensure normal head formation. In this study, we identify five small subsets of progenitors expressing the transcription factor dbx1 in the cephalic region of developing mouse embryos at E8.5. Using genetic tracing we show that dbx1-expressing cells and their progeny have a modest contribution to the forebrain and face tissues. However, their genetic ablation triggers extensive and non cell-autonomous apoptosis as well as a decrease in proliferation in surrounding tissues, resulting in the progressive loss of most of the forebrain and frontonasal structures. Targeted ablation of the different subsets reveals that the very first dbx1-expressing progenitors are critically required for the survival of anterior neural tissues, the production and/or migration of cephalic neural crest cells and, ultimately, forebrain formation. In addition, we find that the other subsets, generated at slightly later stages, each play a specific function during head development and that their coordinated activity is required for accurate craniofacial morphogenesis. Our results demonstrate that dbx1-expressing cells have a unique function during head development, notably by controlling cell survival in a non cell-autonomous manner.

PMID 21552538


The role of the transcription factor Rbpj in the development of dorsal root ganglia

Neural Dev. 2011 Apr 21;6:14. doi: 10.1186/1749-8104-6-14.

Hu ZL, Shi M, Huang Y, Zheng MH, Pei Z, Chen JY, Han H, Ding YQ. Source Department of Anatomy and Neurobiology, Tongji University School of Medicine, Shanghai, China. huzelan@hotmail.com

Abstract

BACKGROUND: The dorsal root ganglion (DRG) is composed of well-characterized populations of sensory neurons and glia derived from a common pool of neural crest stem cells (NCCs), and is a good system to study the mechanisms of neurogenesis and gliogenesis. Notch signaling is known to play important roles in DRG development, but the full scope of Notch functions in mammalian DRG development remains poorly understood.

RESULTS: In the present study, we used Wnt1-Cre to conditionally inactivate the transcription factor Rbpj, a critical integrator of activation signals from all Notch receptors, in NCCs and their derived cells. Deletion of Rbpj caused the up-regulation of NeuroD1 and precocious neurogenesis in DRG early development but led to an eventual deficit of sensory neurons at later stages, due to reduced cell proliferation and abnormal cell death. In addition, gliogenesis was delayed initially, but a near-complete loss of glia was observed finally in Rbpj-deficient DRG. Furthermore, we found P75 and Sox10, which are normally expressed exclusively in neuronal and glial progenitors of the DRG after the NCCs have completed their migration, were co-expressed in many cells of the DRG of Rbpj conditional knock-out mice.

CONCLUSIONS: Our data indicate that Rbpj-mediated canonical Notch signaling inhibits DRG neuronal differentiation, possibly by regulating NeuroD1 expression, and is required for DRG gliogenesis in vivo.

PMID 21510873

2010

Analysis of early human neural crest development

Dev Biol. 2010 Aug 15;344(2):578-92. Epub 2010 May 15.

Betters E, Liu Y, Kjaeldgaard A, Sundström E, García-Castro MI. Source Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520-8103, USA.

Abstract

The outstanding migration and differentiation capacities of neural crest cells (NCCs) have fascinated scientists since Wilhelm His described this cell population in 1868. Today, after intense research using vertebrate model organisms, we have gained considerable knowledge regarding the origin, migration and differentiation of NCCs. However, our understanding of NCC development in human embryos remains largely uncharacterized, despite the role the neural crest plays in several human pathologies. Here, we report for the first time the expression of a battery of molecular markers before, during, or following NCC migration in human embryos from Carnegie Stages (CS) 12 to 18. Our work demonstrates the expression of Sox9, Sox10 and Pax3 transcription factors in premigratory NCCs, while actively migrating NCCs display the additional transcription factors Pax7 and AP-2alpha. Importantly, while HNK-1 labels few migrating NCCs, p75(NTR) labels a large proportion of this population. However, the broad expression of p75(NTR) - and other markers - beyond the neural crest stresses the need for the identification of additional markers to improve our capacity to investigate human NCC development, and to enable the generation of better diagnostic and therapeutic tools.

Copyright 2010 Elsevier Inc. All rights reserved.

PMID 20478300

http://www.sciencedirect.com/science/article/pii/S0012160610002988

Early regulative ability of the neuroepithelium to form cardiac neural crest

Dev Biol. 2010 Nov 1.

Ezin AM, Sechrist JW, Zah A, Bronner M, Fraser SE.

Abstract The cardiac neural crest (arising from the level of hindbrain rhombomeres 6-8) contributes to the septation of the cardiac outflow tract and the formation of aortic arches. Removal of this population after neural tube closure results in severe septation defects in the chick, reminiscent of human birth defects. Because neural crest cells from other axial levels have regenerative capacity, we asked whether the cardiac neural crest might also regenerate at early stages in a manner that declines with time. Accordingly, we find that ablation of presumptive cardiac crest at stage 7, as the neural folds elevate, results in reformation of migrating cardiac neural crest by stage 13. Fate mapping reveals that the new population derives largely from the neuroepithelium ventral and rostral to the ablation. The stage of ablation dictates the competence of residual tissue to regulate and regenerate, as this capacity is lost by stage 9, consistent with previous reports. These findings suggest that there is a temporal window during which the presumptive cardiac neural crest has the capacity to regulate and regenerate, but this regenerative ability is lost earlier than in other neural crest populations.

Copyright © 2010 Elsevier Inc. All rights reserved. PMID: 21047505 http://www.ncbi.nlm.nih.gov/pubmed/21047505


Glial versus melanocyte cell fate choice: Schwann cell precursors as a cellular origin of melanocytes

Cell Mol Life Sci. 2010 Sep;67(18):3037-55. Epub 2010 May 9.

Adameyko I, Lallemend F.

Unit of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Scheeles väg 1-A1-plan2, 171 77, Stockholm, Sweden. igor.adameyko@ki.se Abstract Melanocytes and Schwann cells are derived from the multipotent population of neural crest cells. Although both cell types were thought to be generated through completely distinct pathways and molecular processes, a recent study has revealed that these different cell types are intimately interconnected far beyond previously postulated limits in that they share a common post-neural crest progenitor, i.e. the Schwann cell precursor. This finding raises interesting questions about the lineage relationships of hitherto unrelated cell types such as melanocytes and Schwann cells, and may provide clinical insights into mechanisms of pigmentation disorders and for cancer involving Schwann cells and melanocytes.

PMID: 20454996

Sox10-Venus mice: a new tool for real-time labeling of neural crest lineage cells and oligodendrocytes

Molecular Brain 2010, 3:31 doi:10.1186/1756-6606-3-31

  • Sox-E is the earliest marker of a subset of cells at the border of the neural plate that will give rise to NC-lineage cells
    • see Haldin CE, LaBonne C: SoxE factors as multifunctional neural crest regulatory factors. Int J Biochem Cell Biol 2010, 42:441-444.

2009

Schwann cell precursors from nerve innervation are a cellular origin of melanocytes in skin

Cell. 2009 Oct 16;139(2):366-79.

Adameyko I, Lallemend F, Aquino JB, Pereira JA, Topilko P, Müller T, Fritz N, Beljajeva A, Mochii M, Liste I, Usoskin D, Suter U, Birchmeier C, Ernfors P.

Unit of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, 17177 Stockholm, Sweden. Abstract Current opinion holds that pigment cells, melanocytes, are derived from neural crest cells produced at the dorsal neural tube and that migrate under the epidermis to populate all parts of the skin. Here, we identify growing nerves projecting throughout the body as a stem/progenitor niche containing Schwann cell precursors (SCPs) from which large numbers of skin melanocytes originate. SCPs arise as a result of lack of neuronal specification by Hmx1 homeobox gene function in the neural crest ventral migratory pathway. Schwann cell and melanocyte development share signaling molecules with both the glial and melanocyte cell fates intimately linked to nerve contact and regulated in an opposing manner by Neuregulin and soluble signals including insulin-like growth factor and platelet-derived growth factor. These results reveal SCPs as a cellular origin of melanocytes, and have broad implications on the molecular mechanisms regulating skin pigmentation during development, in health and pigmentation disorders.

PMID: 19837037

Relationship between neural crest cells and cranial mesoderm during head muscle development

PLoS One. 2009;4(2):e4381. Epub 2009 Feb 9. Grenier J, Teillet MA, Grifone R, Kelly RG, Duprez D. CNRS, UMR 7622 Biologie Moléculaire et Cellulaire du Développement, Université Pierre et Marie Curie, Paris, France. Abstract BACKGROUND: In vertebrates, the skeletal elements of the jaw, together with the connective tissues and tendons, originate from neural crest cells, while the associated muscles derive mainly from cranial mesoderm. Previous studies have shown that neural crest cells migrate in close association with cranial mesoderm and then circumscribe but do not penetrate the core of muscle precursor cells of the branchial arches at early stages of development, thus defining a sharp boundary between neural crest cells and mesodermal muscle progenitor cells. Tendons constitute one of the neural crest derivatives likely to interact with muscle formation. However, head tendon formation has not been studied, nor have tendon and muscle interactions in the head. METHODOLOGY/PRINCIPAL FINDINGS: Reinvestigation of the relationship between cranial neural crest cells and muscle precursor cells during development of the first branchial arch, using quail/chick chimeras and molecular markers revealed several novel features concerning the interface between neural crest cells and mesoderm. We observed that neural crest cells migrate into the cephalic mesoderm containing myogenic precursor cells, leading to the presence of neural crest cells inside the mesodermal core of the first branchial arch. We have also established that all the forming tendons associated with branchiomeric and eye muscles are of neural crest origin and express the Scleraxis marker in chick and mouse embryos. Moreover, analysis of Scleraxis expression in the absence of branchiomeric muscles in Tbx1(-/-) mutant mice, showed that muscles are not necessary for the initiation of tendon formation but are required for further tendon development. CONCLUSIONS/SIGNIFICANCE: This results show that neural crest cells and muscle progenitor cells are more extensively mixed than previously believed during arch development. In addition, our results show that interactions between muscles and tendons during craniofacial development are similar to those observed in the limb, despite the distinct embryological origin of these cell types in the head. PMID: 19198652

http://www.ncbi.nlm.nih.gov/pubmed/19198652

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0004381


Merkel cells as putative regulatory cells in skin disorders: an in vitro study

PLoS One. 2009 Aug 11;4(8):e6528.

Boulais N, Pereira U, Lebonvallet N, Gobin E, Dorange G, Rougier N, Chesne C, Misery L. Source University of Brest, EA4326, Brest, France. Abstract Merkel cells (MCs) are involved in mechanoreception, but several lines of evidence suggest that they may also participate in skin disorders through the release of neuropeptides and hormones. In addition, MC hyperplasias have been reported in inflammatory skin diseases. However, neither proliferation nor reactions to the epidermal environment have been demonstrated. We established a culture model enriched in swine MCs to analyze their proliferative capability and to discover MC survival factors and modulators of MC neuroendocrine properties. In culture, MCs reacted to bFGF by extending outgrowths. Conversely, neurotrophins failed to induce cell spreading, suggesting that they do not act as a growth factor for MCs. For the first time, we provide evidence of proliferation in culture through Ki-67 immunoreactivity. We also found that MCs reacted to histamine or activation of the proton gated/osmoreceptor TRPV4 by releasing vasoactive intestinal peptide (VIP). Since VIP is involved in many pathophysiological processes, its release suggests a putative regulatory role for MCs in skin disorders. Moreover, in contrast to mechanotransduction, neuropeptide exocytosis was Ca(2+)-independent, as inhibition of Ca(2+) channels or culture in the absence of Ca(2+) failed to decrease the amount of VIP released. We conclude that neuropeptide release and neurotransmitter exocytosis may be two distinct pathways that are differentially regulated.

PMID: 19668696 http://www.ncbi.nlm.nih.gov/pubmed/19668696

2008

Neural crest origin of perivascular mesenchyme in the adult thymus

J Immunol. 2008 Apr 15;180(8):5344-51.

Müller SM, Stolt CC, Terszowski G, Blum C, Amagai T, Kessaris N, Iannarelli P, Richardson WD, Wegner M, Rodewald HR.

Institute for Immunology, University of Ulm, Ulm, Germany.

Abstract

The endodermal epithelial thymus anlage develops in tight association with neural crest (NC)-derived mesenchyme. This epithelial-NC interaction is crucial for thymus development, but it is not known how NC supports thymus development or whether NC cells or their progeny make any significant contribution to the adult thymus. By nude mouse blastocyst complementation and by cell surface phenotype, we could previously separate thymus stroma into Foxn1-dependent epithelial cells and a Foxn1-independent mesenchymal cell population. These mesenchymal cells expressed vascular endothelial growth factor-A, and contributed to thymus vascularization. These data suggested a physical or functional association with thymic blood vessels, but the origin, location in the thymus, and function of these stromal cells remained unknown. Using a transgenic mouse expressing Cre recombinase in premigratory NC (Sox10-Cre), we have now fate-mapped the majority of these adult mesenchymal cells to a NC origin. NC-derived cells represent tightly vessel-associated pericytes that are sandwiched between endothelium and epithelium along the entire thymus vasculature. The ontogenetic, phenotypic, and positional definition of this distinct perivascular mesenchymal compartment provides a cellular basis for the role of NC in thymus development and possibly maintenance, and might be useful to address properties of the endothelial-epithelial barrier in the adult thymus.

PMID: 18390716

http://www.jimmunol.org/content/180/8/5344.long

2007

The development of the neural crest in the human

J Anat. 2007 Sep;211(3):335-51.

O'Rahilly R, Müller F.

School of Medicine, University of California, Davis, California, USA.

Abstract

The first systematic account of the neural crest in the human has been prepared after an investigation of 185 serially sectioned staged embryos, aided by graphic reconstructions. As many as fourteen named topographical subdivisions of the crest were identified and eight of them give origin to ganglia (Table 2). Significant findings in the human include the following.

(1) An indication of mesencephalic neural crest is discernible already at stage 9, and trigeminal, facial, and postotic components can be detected at stage 10.

(2) Crest was not observed at the level of diencephalon 2. Although pre-otic crest from the neural folds is at first continuous (stage 10), crest-free zones are soon observable (stage 11) in Rh.1, 3, and 5.

(3) Emigration of cranial neural crest from the neural folds at the neurosomatic junction begins before closure of the rostral neuropore, and later crest cells do not accumulate above the neural tube.

(4) The trigeminal, facial, glossopharyngeal and vagal ganglia, which develop from crest that emigrates before the neural folds have fused, continue to receive contributions from the roof plate of the neural tube after fusion of the folds.

(5) The nasal crest and the terminalis-vomeronasal complex are the last components of the cranial crest to appear (at stage 13) and they persist longer.

(6) The optic, mesencephalic, isthmic, accessory, and hypoglossal crest do not form ganglia. Cervical ganglion 1 is separated early from the neural crest and is not a Froriep ganglion.

(7) The cranial ganglia derived from neural crest show a specific relationship to individual neuromeres, and rhombomeres are better landmarks than the otic primordium, which descends during stages 9-14.

(8) Epipharyngeal placodes of the pharyngeal arches contribute to cranial ganglia, although that of arch 1 is not typical.

(9) The neural crest from rhombomeres 6 and 7 that migrates to pharyngeal arch 3 and from there rostrad to the truncus arteriosus at stage 12 is identified here, for the first time in the human, as the cardiac crest.

(10) The hypoglossal crest provides cells that accompany those of myotomes 1-4 and form the hypoglossal cell cord at stages 13 and 14.

(11) The occipital crest, which is related to somites 1-4 in the human, differs from the spinal mainly in that it does not develop ganglia.

(12) The occipital and spinal portions of the crest migrate dorsoventrad and appear to traverse the sclerotomes before the differentiation into loose and dense zones in the latter.

(13) Embryonic examples of synophthalmia and anencephaly are cited to emphasize the role of the neural crest in the development of cranial ganglia and the skull.

PMID 17848161

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2375817

http://onlinelibrary.wiley.com/doi/10.1111/j.1469-7580.2007.00773.x/abstract

Model systems for the study of heart development and disease. Cardiac neural crest and conotruncal malformations

Semin Cell Dev Biol. 2007 Feb;18(1):101-10. Epub 2006 Dec 19.

Hutson MR, Kirby ML. Source Department of Pediatrics, Bell Building, Room 157, Neonatology, Box 3179, Duke University Medical Center, Durham, NC 27710, United States. mhutson@duke.edu

Abstract

Neural crest cells are multipotential cells that delaminate from the dorsal neural tube and migrate widely throughout the body. A subregion of the cranial neural crest originating between the otocyst and somite 3 has been called "cardiac neural crest" because of the importance of these cells in heart development. Much of what we know about the contribution and function of the cardiac neural crest in cardiovascular development has been learned in the chick embryo using quail-chick chimeras to study neural crest migration and derivatives as well as using ablation of premigratory neural crest cells to study their function. These studies show that cardiac neural crest cells are absolutely required to form the aorticopulmonary septum dividing the cardiac arterial pole into systemic and pulmonary circulations. They support the normal development and patterning of derivatives of the caudal pharyngeal arches and pouches, including the great arteries and the thymus, thyroid and parathyroids. Recently, cardiac neural crest cells have been shown to modulate signaling in the pharynx during the lengthening of the outflow tract by the secondary heart field. Most of the genes associated with cardiac neural crest function have been identified using mouse models. These studies show that the neural crest cells may not be the direct cause of abnormal cardiovascular development but they are a major component in the complex tissue interactions in the caudal pharynx and outflow tract. Since, cardiac neural crest cells span from the caudal pharynx into the outflow tract, they are especially susceptible to any perturbation in or by other cells in these regions. Thus, understanding congenital cardiac outflow malformations in human sequences of malformations as represented by the DiGeorge syndrome will necessarily require understanding development of the cardiac neural crest.

PMID 17224285

2005

Neural crest origins of the neck and shoulder

Nature. 2005 Jul 21;436(7049):347-55. Matsuoka T, Ahlberg PE, Kessaris N, Iannarelli P, Dennehy U, Richardson WD, McMahon AP, Koentges G.

Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT, UK.

Abstract The neck and shoulder region of vertebrates has undergone a complex evolutionary history. To identify its underlying mechanisms we map the destinations of embryonic neural crest and mesodermal stem cells using Cre-recombinase-mediated transgenesis. The single-cell resolution of this genetic labelling reveals cryptic cell boundaries traversing the seemingly homogeneous skeleton of the neck and shoulders. Within this assembly of bones and muscles we discern a precise code of connectivity that mesenchymal stem cells of both neural crest and mesodermal origin obey as they form muscle scaffolds. The neural crest anchors the head onto the anterior lining of the shoulder girdle, while a Hox-gene-controlled mesoderm links trunk muscles to the posterior neck and shoulder skeleton. The skeleton that we identify as neural crest-derived is specifically affected in human Klippel-Feil syndrome, Sprengel's deformity and Arnold-Chiari I/II malformation, providing insights into their likely aetiology. We identify genes involved in the cellular modularity of the neck and shoulder skeleton and propose a new method for determining skeletal homologies that is based on muscle attachments. This has allowed us to trace the whereabouts of the cleithrum, the major shoulder bone of extinct land vertebrate ancestors, which seems to survive as the scapular spine in living mammals.

PMID 16034409

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1352163


Compound developmental eye disorders following inactivation of TGFbeta signaling in neural-crest stem cells

J Biol. 2005;4(3):11. Epub 2005 Dec 14.

Ittner LM, Wurdak H, Schwerdtfeger K, Kunz T, Ille F, Leveen P, Hjalt TA, Suter U, Karlsson S, Hafezi F, Born W, Sommer L. Source Research Laboratory for Calcium Metabolism, Orthopedic University Hospital Balgrist, CH-8008 Zurich, Switzerland.

Abstract

BACKGROUND: Development of the eye depends partly on the periocular mesenchyme derived from the neural crest (NC), but the fate of NC cells in mammalian eye development and the signals coordinating the formation of ocular structures are poorly understood.

RESULTS: Here we reveal distinct NC contributions to both anterior and posterior mesenchymal eye structures and show that TGFbeta signaling in these cells is crucial for normal eye development. In the anterior eye, TGFbeta2 released from the lens is required for the expression of transcription factors Pitx2 and Foxc1 in the NC-derived cornea and in the chamber-angle structures of the eye that control intraocular pressure. TGFbeta enhances Foxc1 and induces Pitx2 expression in cell cultures. As in patients carrying mutations in PITX2 and FOXC1, TGFbeta signal inactivation in NC cells leads to ocular defects characteristic of the human disorder Axenfeld-Rieger's anomaly. In the posterior eye, NC cell-specific inactivation of TGFbeta signaling results in a condition reminiscent of the human disorder persistent hyperplastic primary vitreous. As a secondary effect, retinal patterning is also disturbed in mutant mice.

CONCLUSION: In the developing eye the lens acts as a TGFbeta signaling center that controls the development of eye structures derived from the NC. Defective TGFbeta signal transduction interferes with NC-cell differentiation and survival anterior to the lens and with normal tissue morphogenesis and patterning posterior to the lens. The similarity to developmental eye disorders in humans suggests that defective TGFbeta signal modulation in ocular NC derivatives contributes to the pathophysiology of these diseases.

PMID 16403239

http://jbiol.com/content/4/3/11

1996

Rhombencephalic neural crest segmentation is preserved throughout craniofacial ontogeny

Development. 1996 Oct;122(10):3229-42.

Köntges G, Lumsden A.

MRC Brain Development Programme, Department of Developmental Neurobiology, UMDS, Guy's Hospital, London, UK. Abstract To investigate the influence of hindbrain segmentation on craniofacial patterning we have studied the long term fate of neural crest (NC) subpopulations of individual rhombomeres (r), using quail-chick chimeras. Mapping of all skeletal and muscle connective tissues developing from these small regions revealed several novel features of the cranial neural crest. First, the mandibular arch skeleton has a composite origin in which the proximal elements are r1+r2 derived, whereas more distal ones are exclusively midbrain derived. The most proximal region of the lower jaw is derived from second arch (r4) NC. Second, both the lower jaw and tongue skeleton display an organisation which precisely reflects the rostrocaudal order of segmental crest deployment from the embryonic hindbrain. Third, cryptic intraskeletal boundaries, which do not correspond to anatomical landmarks, form sharply defined interfaces between r1+r2, r4 and r6+r7 crest. Cells that survive the early apoptotic elimination of premigratory NC in r3 and r5 are restricted to tiny contributions within the 2nd arch (r4) skeleton. Fourth, a highly constrained pattern of cranial skeletomuscular connectivity was found that precisely respects the positional origin of its constitutive crest: each rhombomeric population remains coherent throughout ontogeny, forming both the connective tissues of specific muscles and their respective attachment sites onto the neuro- and viscerocranium. Finally, focal clusters of crest cells, confined to the attachment sites of branchial muscles, intrude into the otherwise mesodermal cranial base. In the viscerocranium, an equally strict, rhombomere-specific matching of muscle connective tissues and their attachment sites is found for all branchial and tongue (hypoglossal) muscles. This coherence of segmental crest populations explains how cranial skeletomuscular pattern can be implemented and conserved despite evolutionary changes in the shapes of skeletal elements.

PMID: 8898235