scholarly journals Specification of axial identity by Hoxa2 distinguishes between a phenotypic and molecular ground state in mouse cranial neural crest cells

2021 ◽  
Author(s):  
Irina Pushel ◽  
Paul A Trainor ◽  
Robb Krumlauf
Keyword(s):  
Neural Crest ◽  
Ground State ◽  
Molecular Mechanisms ◽  
Neural Crest Cells ◽  
Pharyngeal Arches ◽  
Transcriptional Signature ◽  
Head Formation ◽  
Phenotypic Transformation ◽  
Cranial Neural Crest Cells ◽  
Molecular Ground State

AbstractHox genes play a key role in head formation by specifying the axial identity of neural crest cells (NCCs) migrating into embryonic pharyngeal arches. In the absence of Hoxa2, NCC derivatives of the second pharyngeal arch (PA2) undergo a homeotic transformation and duplicate structures formed by first arch (PA1) NCCs. Current models postulate that PA1 represents a NCC ‘ground state’ and loss of Hoxa2 causes a reversion of PA2 NCCs to the PA1 ‘ground state’. We use bulk and single-cell RNAseq to investigate the molecular mechanisms driving this phenotypic transformation in the mouse. In Hoxa2-/- mutants, PA2 NCCs generally maintain expression of the PA2 transcriptional signature and fail to strongly upregulate a PA1 transcriptional signature. Our analyses identify putative HOXA2 targets and suggest that subsets of NCCs may respond to HOXA2 activity in distinct manners. This separation of phenotypic and molecular states has significant implications for understanding craniofacial development.

The chinless mutation and neural crest cell interactions in zebrafish jaw development

Development ◽  
1996 ◽  
Vol 122 (5) ◽  
pp. 1417-1426 ◽  
Author(s):  
T.F. Schilling ◽  
C. Walker ◽  
C.B. Kimmel
Keyword(s):  
Neural Crest ◽  
Neural Crest Cell ◽  
Neural Crest Cells ◽  
Paraxial Mesoderm ◽  
Wild Type ◽  
Host Genotype ◽  
Pharyngeal Arches ◽  
Expression Studies ◽  
Gene Expression Studies ◽  
Cranial Neural Crest Cells

During vertebrate development, neural crest cells are thought to pattern many aspects of head organization, including the segmented skeleton and musculature of the jaw and gills. Here we describe mutations at the gene chinless, chn, that disrupt the skeletal fates of neural crest cells in the head of the zebrafish and their interactions with muscle precursors. chn mutants lack neural-crest-derived cartilage and mesoderm-derived muscles in all seven pharyngeal arches. Fate mapping and gene expression studies demonstrate the presence of both undifferentiated cartilage and muscle precursors in mutants. However, chn blocks differentiation directly in neural crest, and not in mesoderm, as revealed by mosaic analyses. Neural crest cells taken from wild-type donor embryos can form cartilage when transplanted into chn mutant hosts and rescue some of the patterning defects of mutant pharyngeal arches. In these cases, cartilage only forms if neural crest is transplanted at least one hour before its migration, suggesting that interactions occur transiently in early jaw precursors. In contrast, transplanted cells in paraxial mesoderm behave according to the host genotype; mutant cells form jaw muscles in a wild-type environment. These results suggest that chn is required for the development of pharyngeal cartilages from cranial neural crest cells and subsequent crest signals that pattern mesodermally derived myocytes.

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 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.

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 Neural crest cells require Meis2 for patterning the mandibular arch via the Sonic hedgehog pathway

Biology Open ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. bio052043
Author(s):  
Jaroslav Fabik ◽  
Katarina Kovacova ◽  
Zbynek Kozmik ◽  
Ondrej Machon
Keyword(s):  
Neural Crest ◽  
Sonic Hedgehog ◽  
Neural Crest Cells ◽  
Ectopic Ossification ◽  
Pharyngeal Arches ◽  
Altered Expression ◽  
Neural Crest Origin ◽  
Cranial Neural Crest Cells ◽  
Craniofacial Defects ◽  
Molecular Signals

ABSTRACTCranial neural crest cells (cNCCs) originate in the anterior neural tube and populate pharyngeal arches in which they contribute to formation of bone and cartilage. This cell population also provides molecular signals for the development of tissues of non-neural crest origin, such as the tongue muscles, teeth enamel or gland epithelium. Here we show that the transcription factor Meis2 is expressed in the oral region of the first pharyngeal arch (PA1) and later in the tongue primordium. Conditional inactivation of Meis2 in cNCCs resulted in loss of Sonic hedgehog signalling in the oropharyngeal epithelium and impaired patterning of PA1 along the lateral–medial and oral–aboral axis. Failure of molecular specification of PA1, illustrated by altered expression of Hand1/2, Dlx5, Barx1, Gsc and other markers, led to hypoplastic tongue and ectopic ossification of the mandible. Meis2-mutant mice thus display craniofacial defects that are reminiscent of several human syndromes and patients with mutations in the Meis2 gene.

Jaw and branchial arch mutants in zebrafish I: branchial arches

Development ◽  
1996 ◽  
Vol 123 (1) ◽  
pp. 329-344 ◽  
Author(s):  
T.F. Schilling ◽  
T. Piotrowski ◽  
H. Grandel ◽  
M. Brand ◽  
C.P. Heisenberg ◽  
...  
Keyword(s):  
Neural Crest ◽  
Zebrafish Embryo ◽  
Neural Crest Cells ◽  
Branchial Arch ◽  
Pigment Cells ◽  
Pharyngeal Arches ◽  
Pectoral Fins ◽  
Branchial Arches ◽  
Group Members ◽  
The Brain

Jaws and branchial arches together are a basic, segmented feature of the vertebrate head. Seven arches develop in the zebrafish embryo (Danio rerio), derived largely from neural crest cells that form the cartilaginous skeleton. In this and the following paper we describe the phenotypes of 109 arch mutants, focusing here on three classes that affect the posterior pharyngeal arches, including the hyoid and five gill-bearing arches. In lockjaw, the hyoid arch is strongly reduced and subsets of branchial arches do not develop. Mutants of a large second class, designated the flathead group, lack several adjacent branchial arches and their associated cartilages. Five alleles at the flathead locus all lead to larvae that lack arches 4–6. Among 34 other flathead group members complementation tests are incomplete, but at least six unique phenotypes can be distinguished. These all delete continuous stretches of adjacent branchial arches and unpaired cartilages in the ventral midline. Many show cell death in the midbrain, from which some neural crest precursors of the arches originate. lockjaw and a few mutants in the flathead group, including pistachio, affect both jaw cartilage and pigmentation, reflecting essential functions of these genes in at least two neural crest lineages. Mutants of a third class, including boxer, dackel and pincher, affect pectoral fins and axonal trajectories in the brain, as well as the arches. Their skeletal phenotypes suggest that they disrupt cartilage morphogenesis in all arches. Our results suggest that there are sets of genes that: (1) specify neural crest cells in groups of adjacent head segments, and (2) function in common genetic pathways in a variety of tissues including the brain, pectoral fins and pigment cells as well as pharyngeal arches.

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