scholarly journals Modulation of β-catenin levels is critical for cranial neural crest patterning and dispersal into first pharyngeal arch

2019 ◽  
Author(s):  
Alok Javali ◽  
Vairavan Laxmanan ◽  
Dasaradhi Palakodeti ◽  
Ramkumar Sambasivan
Keyword(s):  
Neural Crest ◽  
Neural Crest Cells ◽  
Mouse Embryos ◽  
Pharyngeal Arch ◽  
Cranial Neural Crest ◽  
Connective Tissues ◽  
Pharyngeal Arches ◽  
Cell Arrangement ◽  
Cranial Neural Crest Cells

AbstractVertebrate cranial neural crest cells (CNCC) are multipotent. Proximal to the source CNCC form the cranial ganglia. Distally, in the pharyngeal arches, they give rise to the craniofacial skeleton and connective tissues. Fate choices are made as CNCC pattern into distinct destination compartments. In spite of this importance, the mechanism patterning CNCC is poorly defined. Here, we report that a novel β-catenin-controlled switch in the cell arrangement is critical in patterning CNCC. In mouse embryos, at the first pharyngeal arch axial level, membrane β-catenin levels correlate with the extent of cell-cell adhesion and thus, with a collective or a dispersed state of CNCC. Using in vitro human neural crest model and chemical modulators of β-catenin levels, we show a requirement for down-modulating β-catenin for the collective-to-dispersed switch. Similarly, in β-catenin gain of function mutant mouse embryos, CNCC fail to disperse, which may underlie their failure to populate first pharyngeal arch. Thus, we show that β-catenin-mediated regulation of CNCC tissue architecture, a previously underappreciated mechanism, underlies the patterning of CNCC into fate-specific compartments.Summary statementThe report shows a crucial step in cranial neural crest patterning. Neural crest cells invading the pharyngeal arches transition from a collective to a dispersed state. This transition in cell arrangement is dependent on membrane β-catenin levels.

scholarly journals Stage-Dependent Differential Gene Expression Profiles of Cranial Neural Crest Cells Derived from Mouse Induced Pluripotent Stem Cells

2018 ◽  
Author(s):  
Ayano Odashima ◽  
Shoko Onodera ◽  
Akiko Saito ◽  
Takashi Nakamura ◽  
Yuuki Ogihara ◽  
...  
Keyword(s):  
Gene Expression ◽  
Neural Crest ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Neural Crest Cells ◽  
Cranial Neural Crest ◽  
Pharyngeal Arches ◽  
A Disintegrin And Metalloproteinase ◽  
Induced Pluripotent ◽  
Cranial Neural Crest Cells

AbstractCranial neural crest cells (cNCCs) comprise a multipotent population of cells that migrate into the pharyngeal arches of the vertebrate embryo and differentiate into a broad range of derivatives of the craniofacial organs. Consequently, migrating cNCCs are considered as one of the most attractive candidate sources of cells for regenerative medicine. In this study, we analyzed the gene expression profiles of cNCCs at different time points after induction by conducting three independent RNA sequencing experiments. We successfully induced cNCC formation from mouse induced pluripotent stem (miPS) cells by culturing them in neural crest inducing media for 14 days. We found that these cNCCs expressed several neural crest specifier genes but were lacking some previously reported specifiers, such as paired box 3 (Pax3), msh homeobox 1 (Msx1), and Forkhead box D3 (FoxD3), which are presumed to be essential for neural crest development in the embryo. Thus, a distinct molecular network may the control gene expression in miPS-derived cNCCs. We also found that c-Myc, ETS proto-oncogene 1, transcription factor (Ets1), and sex determining region Y-box 10 (Sox10) were only detected at 14 days after induction. Therefore, we assume that these genes would be useful markers for migratory cNCCs induced from miPS cells. Eventually, these cNCCs comprised a broad spectrum of protocadherin (Pcdh) and a disintegrin and metalloproteinase with thrombospondin motifs (Adamts) family proteins, which may be crucial in their migration.

scholarly journals FGF2 promotes skeletogenic differentiation of cranial neural crest cells

Development ◽  
2001 ◽  
Vol 128 (11) ◽  
pp. 2143-2152 ◽  
Author(s):  
Sanjukta Sarkar ◽  
Anita Petiot ◽  
Andrew Copp ◽  
Patrizia Ferretti ◽  
Peter Thorogood
Keyword(s):  
Neural Crest ◽  
Neural Crest Cells ◽  
Dependent Manner ◽  
Cranial Neural Crest ◽  
Fibroblast Growth Factor Receptors ◽  
Tissue Interactions ◽  
Membrane Bone ◽  
Cartilage Differentiation ◽  
Cranial Neural Crest Cells

The cranial neural crest gives rise to most of the skeletal tissues of the skull. Matrix-mediated tissue interactions have been implicated in the skeletogenic differentiation of crest cells, but little is known of the role that growth factors might play in this process. The discovery that mutations in fibroblast growth factor receptors (FGFRs) cause the major craniosynostosis syndromes implicates FGF-mediated signalling in the skeletogenic differentiation of the cranial neural crest. We now show that, in vitro, mesencephalic neural crest cells respond to exogenous FGF2 in a dose-dependent manner, with 0.1 and 1 ng/ml causing enhanced proliferation, and 10 ng/ml inducing cartilage differentiation. In longer-term cultures, both endochondral and membrane bone are formed. FGFR1, FGFR2 and FGFR3 are all detectable by immunohistochemistry in the mesencephalic region, with particularly intense expression at the apices of the neural folds from which the neural crest arises. FGFRs are also expressed by subpopulations of neural crest cells in culture. Collectively, these findings suggest that FGFs are involved in the skeletogenic differentiation of the cranial neural crest.

Early Craniofacial Defects in Zebrafish that Have Reduced Function of a Wnt-Interacting Extracellular Matrix Protein, Tinagl1

2017 ◽  
Vol 54 (4) ◽  
pp. 381-390 ◽  
Author(s):  
Hannah Neiswender ◽  
Sammy Navarre ◽  
David J. Kozlowski ◽  
Ellen K. Lemosy
Keyword(s):  
Neural Crest ◽  
Cleft Lip ◽  
Matrix Protein ◽  
Bone Development ◽  
Neural Crest Cells ◽  
Extracellular Matrix Protein ◽  
Cranial Neural Crest ◽  
Pharyngeal Arches ◽  
Cranial Neural Crest Cells ◽  
Craniofacial Defects

Objective Tinagl1 has a weak genetic association with craniosynostosis, but its functions in cartilage and bone development are unknown. Knockdown of Tinagl1 in zebrafish embryos allowed an initial characterization of its potential effects on craniofacial cartilage development and a test of whether these effects could involve Wnt signaling. Results Tinagl1 knockdown resulted in dose-dependent reductions and defects in ventral pharyngeal arch cartilages as well as the ethmoid plate, a zebrafish correlate to the palate. These defects could be correlated to reduced numbers of cranial neural crest cells in the pharyngeal arches and could be reproduced with comanipulation of Tinagl1 and Wnt3a by morpholino-based knockdown. Conclusions These results suggest that Tinagl1 is required early in the proliferation or migration of cranial neural crest cells and that its effects are mediated via Wnt3a signaling. Because Wnt3a is among the Wnts that contribute to nonsyndromic cleft lip and cleft palate in mouse and man, further investigation of Tinagl1 may help to elucidate mechanisms underlying these disorders.

scholarly journals Augmented BMP signaling commits cranial neural crest cells to a chondrogenic fate by suppressing autophagic β-catenin degradation

2021 ◽  
Vol 14 (665) ◽  
pp. eaaz9368
Author(s):  
Jingwen Yang ◽  
Megumi Kitami ◽  
Haichun Pan ◽  
Masako Toda Nakamura ◽  
Honghao Zhang ◽  
...  
Keyword(s):  
Neural Crest ◽  
Neural Crest Cells ◽  
Bmp Signaling ◽  
Fibrodysplasia Ossificans Progressiva ◽  
Type I ◽  
Cranial Neural Crest ◽  
Connective Tissues ◽  
Multipotent Stem Cells ◽  
Morphogenetic Protein ◽  
Cranial Neural Crest Cells

Cranial neural crest cells (CNCCs) are a population of multipotent stem cells that give rise to craniofacial bone and cartilage during development. Bone morphogenetic protein (BMP) signaling and autophagy have been individually implicated in stem cell homeostasis. Mutations that cause constitutive activation of the BMP type I receptor ACVR1 cause the congenital disorder fibrodysplasia ossificans progressiva (FOP), which is characterized by ectopic cartilage and bone in connective tissues in the trunk and sometimes includes ectopic craniofacial bones. Here, we showed that enhanced BMP signaling through the constitutively activated ACVR1 (ca-ACVR1) in CNCCs in mice induced ectopic cartilage formation in the craniofacial region through an autophagy-dependent mechanism. Enhanced BMP signaling suppressed autophagy by activating mTORC1, thus blocking the autophagic degradation of β-catenin, which, in turn, caused CNCCs to adopt a chondrogenic identity. Transient blockade of mTORC1, reactivation of autophagy, or suppression of Wnt–β-catenin signaling reduced ectopic cartilages in ca-Acvr1 mutants. Our results suggest that BMP signaling and autophagy coordinately regulate β-catenin activity to direct the fate of CNCCs during craniofacial development. These findings may also explain why some patients with FOP develop ectopic bones through endochondral ossification in craniofacial regions.

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