Fate of the mammalian cranial neural crest during tooth and mandibular morphogenesis

Development ◽  
2000 ◽  
Vol 127 (8) ◽  
pp. 1671-1679 ◽  
Author(s):  
Y. Chai ◽  
X. Jiang ◽  
Y. Ito ◽  
P. Bringas ◽  
J. Han ◽  
...  
Keyword(s):  
Neural Crest ◽  
Genetic Manipulation ◽  
Cell Lineage ◽  
Neural Crest Cell ◽  
Neural Crest Cells ◽  
Genetic System ◽  
Branchial Arch ◽  
Mouse Line ◽  
Cranial Neural Crest ◽  
Two Component

Neural crest cells are multipotential stem cells that contribute extensively to vertebrate development and give rise to various cell and tissue types. Determination of the fate of mammalian neural crest has been inhibited by the lack of appropriate markers. Here, we make use of a two-component genetic system for indelibly marking the progeny of the cranial neural crest during tooth and mandible development. In the first mouse line, Cre recombinase is expressed under the control of the Wnt1 promoter as a transgene. Significantly, Wnt1 transgene expression is limited to the migrating neural crest cells that are derived from the dorsal CNS. The second mouse line, the ROSA26 conditional reporter (R26R), serves as a substrate for the Cre-mediated recombination. Using this two-component genetic system, we have systematically followed the migration and differentiation of the cranial neural crest (CNC) cells from E9.5 to 6 weeks after birth. Our results demonstrate, for the first time, that CNC cells contribute to the formation of condensed dental mesenchyme, dental papilla, odontoblasts, dentine matrix, pulp, cementum, periodontal ligaments, chondrocytes in Meckel's cartilage, mandible, the articulating disc of temporomandibular joint and branchial arch nerve ganglia. More importantly, there is a dynamic distribution of CNC- and non-CNC-derived cells during tooth and mandibular morphogenesis. These results are a first step towards a comprehensive understanding of neural crest cell migration and differentiation during mammalian craniofacial development. Furthermore, this transgenic model also provides a new tool for cell lineage analysis and genetic manipulation of neural-crest-derived components in normal and abnormal embryogenesis.

scholarly journals Connexin 43 impacts the chick premigratory cranial neural crest cell population without affecting the neural crest cell epithelial-to-mesenchymal transition

2019 ◽  
Author(s):  
Karyn Jourdeuil ◽  
Lisa A. Taneyhill
Keyword(s):  
Gap Junctions ◽  
Neural Crest ◽  
Gap Junction ◽  
Neural Crest Cell ◽  
Neural Crest Cells ◽  
Cranial Neural Crest ◽  
Mesenchymal Transition ◽  
Junction Protein ◽  
Cranial Neural Crest Cells ◽  
Crest Cell

ABSTRACTGap junctions are intercellular channels that allow for the diffusion of small ions and solutes between coupled cells. Connexin 43 (Cx43), also known as Gap Junction Protein α1, is the most broadly expressed gap junction protein in vertebrate development. Cx43 is strongly expressed in premigratory cranial neural crest cells and is maintained throughout the neural crest cell epithelial-to-mesenchymal transition (EMT), but its function in these cells is not known. To this end, we have used a combination of in vivo and ex vivo live imaging with confocal microscopy, immunohistochemistry, and functional assays to assess gap junction formation, and Cx43 function, in chick premigratory cranial neural crest cells. Our results demonstrate that gap junctions exist between chick premigratory and migratory cranial neural crest cells, with Cx43 depletion inhibiting the function of gap junctions. While a reduction in Cx43 levels just prior to neural crest cell EMT did not affect EMT and subsequent emigration of neural crest cells from the neural tube, the size of the premigratory neural crest cell domain was decreased in the absence of any changes in cell proliferation or death. Collectively, these data identify a role for Cx43 within the chick premigratory cranial neural crest cell population prior to EMT and migration.

scholarly journals Chick cranial neural crest cells migrate by progressively refining the polarity of their protrusions

2017 ◽  
Author(s):  
Miriam A. Genuth ◽  
Christopher D.C. Allen ◽  
Takashi Mikawa ◽  
Orion D. Weiner
Keyword(s):  
Neural Crest ◽  
Quantitative Imaging ◽  
Cell Movement ◽  
Neural Crest Cells ◽  
Branchial Arch ◽  
Cranial Neural Crest ◽  
Directed Movement ◽  
Morphological Polarity ◽  
Cranial Neural Crest Cells

SummaryIn vivo quantitative imaging reveals that chick cranial neural crest cells throughout the migratory stream are morphologically polarized and migrate by progressively refining the polarity of their protrusions.AbstractTo move directionally, cells can bias the generation of protrusions or select among randomly generated protrusions. Here we use 3D two-photon imaging of chick branchial arch 2 directed neural crest cells to probe how these mechanisms contribute to directed movement, whether a subset or the majority of cells polarize during movement, and how the different classes of protrusions relate to one another. We find that cells throughout the stream are morphologically polarized along the direction of overall stream movement and that there is a progressive sharpening of the morphological polarity program. Neural crest cells have weak spatial biases in filopodia generation and lifetime. Local bursts of filopodial generation precede the generation of larger protrusions. These larger protrusions are more spatially biased than the filopodia, and the subset of protrusions that power motility are the most polarized of all. Orientation rather than position is the best correlate of the protrusions that are selected for cell movement. This progressive polarity refinement strategy may enable neural crest cells to efficiently explore their environment and migrate accurately in the face of noisy guidance cues.

5-HT2B receptor-mediated serotonin morphogenetic functions in mouse cranial neural crest and myocardiac cells

Development ◽  
1997 ◽  
Vol 124 (9) ◽  
pp. 1745-1755 ◽  
Author(s):  
D.S. Choi ◽  
S.J. Ward ◽  
N. Messaddeq ◽  
J.M. Launay ◽  
L. Maroteaux
Keyword(s):  
Neural Crest ◽  
Mrna Expression ◽  
Molecular Mechanisms ◽  
In Situ Hybridisation ◽  
Neural Crest Cell ◽  
Neural Crest Cells ◽  
Ventricular Myocardium ◽  
Receptor Subtypes ◽  
Cranial Neural Crest ◽  
Receptor Mrna

During embryogenesis, serotonin has been reported to be involved in craniofacial and cardiovascular morphogenesis. The detailed molecular mechanisms underlying these functions, however remain unknown. From mouse and human species, we have recently reported the cloning of 5-HT2B receptors which share signal transduction pathways with other 5-HT2 receptor subtypes (5-HT2A and 5-HT2C). In addition to phospholipase C stimulation, it appears that these three subtypes of receptor transduce a common serotonin-induced mitogenic activity, which could be important for cell differentiation and proliferation. We have first investigated the expression of 5-HT2 receptor mRNAs in the mouse embryo. Interestingly, a peak of 5-HT2B receptor mRNA expression was detected 8–9 days postcoitum, whereas there was only low level 5-HT2A and no 5-HT2C receptor mRNA expression at this stage. Expression of this receptor was confirmed by binding assays using a 5-HT2-specific ligand which revealed a peak of binding to membrane preparations from 9 days postcoitum embryos. In addition, whole mount in situ hybridisation and immunohistochemistry on similar stage embryos detected 5-HT2B expression in neural crest cells, heart myocardium and somites. The requirement for functional 5-HT2B receptors between 8 and 9 days postcoitum is supported by culture of embryos exposed to 5-HT2-specific ligands; 5-HT2B high-affinity antagonist such as ritanserin, induced morphological defects in the cephalic region, heart and neural tube. These antagonistic treatments interfere with cranial neural crest cell migration, induce their apoptosis, and are responsible for abnormal sarcomeric organisation of the subepicardial layer and for the absence of the trabecular cell layer in the ventricular myocardium. This report indicates for the first time that 5-HT2B receptors are actively mediating the action of serotonin on embryonic morphogenesis, probably by preventing the differentiation of cranial neural crest cells and myocardial precursor cells.

Signalling between the hindbrain and paraxial tissues dictates neural crest migration pathways

Development ◽  
2002 ◽  
Vol 129 (2) ◽  
pp. 433-442 ◽  
Author(s):  
Paul A. Trainor ◽  
Dorothy Sobieszczuk ◽  
David Wilkinson ◽  
Robb Krumlauf
Keyword(s):  
Cell Migration ◽  
Neural Crest ◽  
Neural Crest Cell ◽  
Neural Crest Cells ◽  
Cranial Neural Crest ◽  
Branchial Arches ◽  
Neural Crest Cell Migration ◽  
And Migration ◽  
Migration Pathways ◽  
Crest Cell

Cranial neural crest cells are a pluripotent population of cells derived from the neural tube that migrate into the branchial arches to generate the distinctive bone, connective tissue and peripheral nervous system components characteristic of the vertebrate head. The highly conserved segmental organisation of the vertebrate hindbrain plays an important role in pattering the pathways of neural crest cell migration and in generating the distinct or separate streams of crest cells that form unique structures in each arch. We have used focal injections of DiI into the developing mouse hindbrain in combination with in vitro whole embryo culture to map the patterns of cranial neural crest cell migration into the developing branchial arches. Our results show that mouse hindbrain-derived neural crest cells migrate in three segregated streams adjacent to the even-numbered rhombomeres into the branchial arches, and each stream contains contributions of cells from three rhombomeres in a pattern very similar to that observed in the chick embryo. There are clear neural crest-free zones adjacent to r3 and r5. Furthermore, using grafting and lineage-tracing techniques in cultured mouse embryos to investigate the differential ability of odd and even-numbered segments to generate neural crest cells, we find that odd and even segments have an intrinsic ability to produce equivalent numbers of neural crest cells. This implies that inter-rhombomeric signalling is less important than combinatorial interactions between the hindbrain and the adjacent arch environment in specific regions, in the process of restricting the generation and migration of neural crest cells. This creates crest-free territories and suggests that tissue interactions established during development and patterning of the branchial arches may set up signals that the neural plate is primed to interpret during the progressive events leading to the delamination and migration of neural crest cells. Using interspecies grafting experiments between mouse and chick embryos, we have shown that this process forms part of a conserved mechanism for generating neural crest-free zones and contributing to the separation of migrating crest populations with distinct Hox expression during vertebrate head development.

scholarly journals Cadherin-6B is proteolytically processed during epithelial-to-mesenchymal transitions of the cranial neural crest

2014 ◽  
Vol 25 (1) ◽  
pp. 41-54 ◽  
Author(s):  
Andrew T. Schiffmacher ◽  
Rangarajan Padmanabhan ◽  
Sharon Jhingory ◽  
Lisa A. Taneyhill
Keyword(s):  
Neural Crest ◽  
Epithelial To Mesenchymal Transition ◽  
Neural Crest Cell ◽  
Neural Crest Cells ◽  
Spatiotemporal Pattern ◽  
Cranial Neural Crest ◽  
Mesenchymal Transition ◽  
Crest Cell

The epithelial-to-mesenchymal transition (EMT) is a highly coordinated process underlying both development and disease. Premigratory neural crest cells undergo EMT, migrate away from the neural tube, and differentiate into diverse cell types during vertebrate embryogenesis. Adherens junction disassembly within premigratory neural crest cells is one component of EMT and, in chick cranial neural crest cells, involves cadherin-6B (Cad6B) down-regulation. Whereas Cad6B transcription is repressed by Snail2, the rapid loss of Cad6B protein during EMT is suggestive of posttranslational mechanisms that promote Cad6B turnover. For the first time in vivo, we demonstrate Cad6B proteolysis during neural crest cell EMT, which generates a Cad6B N-terminal fragment (NTF) and two C-terminal fragments (CTF1/2). Coexpression of relevant proteases with Cad6B in vitro shows that a disintegrin and metalloproteinases (ADAMs) ADAM10 and ADAM19, together with γ-secretase, cleave Cad6B to produce the NTF and CTFs previously observed in vivo. Of importance, both ADAMs and γ-secretase are expressed in the appropriate spatiotemporal pattern in vivo to proteolytically process Cad6B. Overexpression or depletion of either ADAM within premigratory neural crest cells prematurely reduces or maintains Cad6B, respectively. Collectively these results suggest a dual mechanism for Cad6B proteolysis involving two ADAMs, along with γ-secretase, during cranial neural crest cell EMT.

scholarly journals MAPRE2 mutations result in altered human cranial neural crest migration, underlying craniofacial malformations in CSC-KT syndrome

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Cedric Thues ◽  
Jorge S. Valadas ◽  
Liesbeth Deaulmerie ◽  
Ann Geens ◽  
Amit K. Chouhan ◽  
...  
Keyword(s):  
Neural Crest ◽  
Induced Pluripotent Stem Cell ◽  
Neural Crest Cells ◽  
Branchial Arch ◽  
Cellular Migration ◽  
Cranial Neural Crest ◽  
Craniofacial Malformations ◽  
Neural Crest Migration

AbstractCircumferential skin creases (CSC-KT) is a rare polymalformative syndrome characterised by intellectual disability associated with skin creases on the limbs, and very characteristic craniofacial malformations. Previously, heterozygous and homozygous mutations in MAPRE2 were found to be causal for this disease. MAPRE2 encodes for a member of evolutionary conserved microtubule plus end tracking proteins, the end binding (EB) family. Unlike MAPRE1 and MAPRE3, MAPRE2 is not required for the persistent growth and stabilization of microtubules, but plays a role in other cellular processes such as mitotic progression and regulation of cell adhesion. The mutations identified in MAPRE2 all reside within the calponin homology domain, responsible to track and interact with the plus-end tip of growing microtubules, and previous data showed that altered dosage of MAPRE2 resulted in abnormal branchial arch patterning in zebrafish. In this study, we developed patient derived induced pluripotent stem cell lines for MAPRE2, together with isogenic controls, using CRISPR/Cas9 technology, and differentiated them towards neural crest cells with cranial identity. We show that changes in MAPRE2 lead to alterations in neural crest migration in vitro but also in vivo, following xenotransplantation of neural crest progenitors into developing chicken embryos. In addition, we provide evidence that changes in focal adhesion might underlie the altered cell motility of the MAPRE2 mutant cranial neural crest cells. Our data provide evidence that MAPRE2 is involved in cellular migration of cranial neural crest and offers critical insights into the mechanism underlying the craniofacial dysmorphisms and cleft palate present in CSC-KT patients. This adds the CSC-KT disorder to the growing list of neurocristopathies.

scholarly journals The alx3 gene shapes the zebrafish neurocranium by regulating frontonasal neural crest cell differentiation timing

Development ◽  
2021 ◽  
Vol 148 (7) ◽  
Author(s):  
Jennyfer M. Mitchell ◽  
Juliana Sucharov ◽  
Anthony T. Pulvino ◽  
Elliott P. Brooks ◽  
Austin E. Gillen ◽  
...  
Keyword(s):  
Neural Crest ◽  
Neural Crest Cell ◽  
Neural Crest Cells ◽  
Developmental Timing ◽  
Cranial Neural Crest ◽  
Different Populations ◽  
Cell Subpopulations ◽  
Cranial Neural Crest Cells ◽  
Discrete Populations ◽  
Crest Cell

ABSTRACT During craniofacial development, different populations of cartilage- and bone-forming cells develop in precise locations in the head. Most of these cells are derived from pluripotent cranial neural crest cells and differentiate with distinct developmental timing and cellular morphologies. The mechanisms that divide neural crest cells into discrete populations are not fully understood. Here, we use single-cell RNA sequencing to transcriptomically define different populations of cranial neural crest cells. We discovered that the gene family encoding the Alx transcription factors is enriched in the frontonasal population of neural crest cells. Genetic mutant analyses indicate that alx3 functions to regulate the distinct differentiation timing and cellular morphologies among frontonasal neural crest cell subpopulations. This study furthers our understanding of how genes controlling developmental timing shape craniofacial skeletal elements.

Synergy betweenHoxa1andHoxb1: the relationship between arch patterning and the generation of cranial neural crest

Development ◽  
2001 ◽  
Vol 128 (15) ◽  
pp. 3017-3027 ◽  
Author(s):  
Anthony Gavalas ◽  
Paul Trainor ◽  
Linda Ariza-McNaughton ◽  
Robb Krumlauf
Keyword(s):  
Neural Crest ◽  
Double Mutant ◽  
Hox Genes ◽  
Neural Crest Cell ◽  
Neural Crest Cells ◽  
Vital Role ◽  
Cranial Neural Crest ◽  
Double Mutation ◽  
Signalling Molecules ◽  
Arch Neural

Hoxa1 and Hoxb1 have overlapping synergistic roles in patterning the hindbrain and cranial neural crest cells. The combination of an ectoderm-specific regulatory mutation in the Hoxb1 locus and the Hoxa1 mutant genetic background results in an ectoderm-specific double mutation, leaving the other germ layers impaired only in Hoxa1 function. This has allowed us to examine neural crest and arch patterning defects that originate exclusively from the neuroepithelium as a result of the simultaneous loss of Hoxa1 and Hoxb1 in this tissue. Using molecular and lineage analysis in this double mutant background we demonstrate that presumptive rhombomere 4, the major site of origin of the second pharyngeal arch neural crest, is reduced in size and has lost the ability to generate neural crest cells. Grafting experiments using wild-type cells in cultured normal or double mutant mouse embryos demonstrate that this is a cell-autonomous defect, suggesting that the formation or generation of cranial neural crest has been uncoupled from segmental identity in these mutants. Furthermore, we show that loss of the second arch neural crest population does not have any adverse consequences on early patterning of the second arch. Signalling molecules are expressed correctly and pharyngeal pouch and epibranchial placode formation are unaffected. There are no signs of excessive cell death or loss of proliferation in the epithelium of the second arch, suggesting that the neural crest cells are not the source of any indispensable mitogenic or survival signals. These results illustrate that Hox genes are not only necessary for proper axial specification of the neural crest but that they also play a vital role in the generation of this population itself. Furthermore, they demonstrate that early patterning of the separate components of the pharyngeal arches can proceed independently of neural crest cell migration.

scholarly journals Dissection, Culture and Analysis of Primary Cranial Neural Crest Cells from Mouse for the Study of Neural Crest Cell Delamination and Migration

10.3791/60051 ◽  
2019 ◽  
Author(s):  
Sandra Guadalupe Gonzalez Malagon ◽  
Lisa Dobson ◽  
Anna M Lopez Muñoz ◽  
Marcus Dawson ◽  
William Barrell ◽  
...  
Keyword(s):  
Neural Crest ◽  
Neural Crest Cell ◽  
Neural Crest Cells ◽  
Cranial Neural Crest ◽  
And Migration ◽  
Cranial Neural Crest Cells ◽  
Crest Cell
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