BMP signaling is essential for development of skeletogenic and neurogenic cranial neural crest

Development ◽  
2000 ◽  
Vol 127 (5) ◽  
pp. 1095-1104 ◽  
Author(s):  
B. Kanzler ◽  
R.K. Foreman ◽  
P.A. Labosky ◽  
M. Mallo
Keyword(s):  
Transgenic Mice ◽  
Neural Crest ◽  
Essential Role ◽  
Expression Patterns ◽  
Neural Crest Cells ◽  
Bmp Signaling ◽  
Cranial Neural Crest ◽  
Temporal Expression ◽  
Branchial Arches

BMP signaling is essential for a wide variety of developmental processes. To evaluate the role of Bmp2/4 in cranial neural crest (CNC) formation or differentiation after its migration into the branchial arches, we used Xnoggin to block their activities in specific areas of the CNC in transgenic mice. This resulted in depletion of CNC cells from the targeted areas. As a consequence, the branchial arches normally populated by the affected neural crest cells were hypomorphic and their skeletal and neural derivatives failed to develop. In further analyses, we have identified Bmp2 as the factor required for production of migratory cranial neural crest. Its spatial and temporal expression patterns mirror CNC emergence and Bmp2 mutant embryos lack both branchial arches and detectable migratory CNC cells. Our results provide functional evidence for an essential role of BMP signaling in CNC development.

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 Over-activation of BMP signaling in neural crest cells precipitates heart outflow tract septation

2019 ◽  
Author(s):  
Jean-François Darrigrand ◽  
Mariana Valente ◽  
Pauline Martinez ◽  
Glenda Comai ◽  
Maxime Petit ◽  
...  
Keyword(s):  
Neural Crest ◽  
Bone Morphogenetic Proteins ◽  
3D Imaging ◽  
Neural Crest Cells ◽  
Outflow Tract ◽  
Bmp Signaling ◽  
Pulmonary Artery Obstruction ◽  
Artery Obstruction ◽  
Embryonic Death

SummaryEstablishment of separated pulmonary and systemic circulations in vertebrates relies on the key role of neural crest cells (NCC) for the septation of the embryonic cardiac outflow tract (OFT). Absence of NCCs induces OFT septation defects, analogous to a loss of Bone Morphogenetic Proteins (BMPs) activity, though it remains unclear how BMPs control cardiac NCC differentiation and behaviour. To address this question, we monitored cardiac NCC state upon gain in BMP signaling, caused by the deletion of Dullard, using 3D-imaging and single cell transcriptomics. Specific loss of Dullard in the NCC results in premature OFT septation, pulmonary artery obstruction and embryonic death. This is caused by uncontrolled NCC convergence towards the endocardium and asymmetrical myocardial differentiation, promoted by elevated levels of the guiding cue Sema3c and decreased levels in mesenchymal trait markers. Furthermore, we unraveled the molecular basis of the zipper-like OFT septation where graded Sema3c expression follow a gradient of BMP activation in NCC along the OFT length.

scholarly journals A novel spalt gene expressed in branchial arches affects the ability of cranial neural crest cells to populate sensory ganglia

2004 ◽  
Vol 1 (1) ◽  
pp. 57-63 ◽  
Author(s):  
MEYER BAREMBAUM ◽  
MARIANNE BRONNER-FRASER
Keyword(s):  
Neural Crest ◽  
Trigeminal Ganglion ◽  
Neural Tube ◽  
Cell Lineage ◽  
Neural Crest Cells ◽  
Cranial Neural Crest ◽  
Facial Skeleton ◽  
Differentiation Markers ◽  
Branchial Arches ◽  
Cranial Neural Crest Cells

Cranial neural crest cells differentiate into diverse derivatives including neurons and glia of the cranial ganglia, and cartilage and bone of the facial skeleton. Here, we explore the function of a novel transcription factor of the spalt family that might be involved in early cell-lineage decisions of the avian neural crest. The chicken spalt4 gene (csal4) is expressed in the neural tube, migrating neural crest, branchial arches and, transiently, in the cranial ectoderm. Later, it is expressed in the mesectodermal, but not neuronal or glial, derivatives of midbrain and hindbrain neural crest. After over-expression by electroporation into the cranial neural tube and neural crest, we observed a marked redistribution of electroporated neural crest cells in the vicinity of the trigeminal ganglion. In control-electroporated embryos, numerous, labeled neural crest cells (∼80% of the population) entered the ganglion, many of which differentiated into neurons. By contrast, few (∼30% of the population) spalt-electroporated neural crest cells entered the trigeminal ganglion. Instead, they localized in the mesenchyme around the ganglionic periphery or continued further ventrally to the branchial arches. Interestingly, little or no expression of differentiation markers for neurons or other cell types was observed in spalt-electroporated neural crest cells.

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.

scholarly journals An Essential Role of Variant Histone H3.3 for Ectomesenchyme Potential of the Cranial Neural Crest

PLoS Genetics ◽  
2012 ◽  
Vol 8 (9) ◽  
pp. e1002938 ◽  
Author(s):  
Samuel G. Cox ◽  
Hyunjung Kim ◽  
Aaron Timothy Garnett ◽  
Daniel Meulemans Medeiros ◽  
Woojin An ◽  
...  
Keyword(s):  
Neural Crest ◽  
Essential Role ◽  
Cranial Neural Crest ◽  
Histone H3.3

scholarly journals Analysis of cranial neural crest migratory pathways in axolotl using cell markers and transplantation

Development ◽  
2000 ◽  
Vol 127 (12) ◽  
pp. 2751-2761 ◽  
Author(s):  
H. Epperlein ◽  
D. Meulemans ◽  
M. Bronner-Fraser ◽  
H. Steinbeisser ◽  
M.A. Selleck
Keyword(s):  
Transcription Factor ◽  
Neural Crest ◽  
Neural Crest Cells ◽  
Branchial Arch ◽  
Cranial Neural Crest ◽  
Branchial Arches ◽  
Trunk Neural Crest ◽  
Cranial Neural Crest Cells ◽  
Random Nature

We have examined the ability of normal and heterotopically transplanted neural crest cells to migrate along cranial neural crest pathways in the axolotl using focal DiI injections and in situ hybridization with the neural crest marker, AP-2. DiI labeling demonstrates that cranial neural crest cells migrate as distinct streams along prescribed pathways to populate the maxillary and mandibular processes of the first branchial arch, the hyoid arch and gill arches 1–4, following migratory pathways similar to those observed in other vertebrates. Another neural crest marker, the transcription factor AP-2, is expressed by premigratory neural crest cells within the neural folds and migrating neural crest cells en route to and within the branchial arches. Rotations of the cranial neural folds suggest that premigratory neural crest cells are not committed to a specific branchial arch fate, but can compensate when displaced short distances from their targets by migrating to a new target arch. In contrast, when cells are displaced far from their original location, they appear unable to respond appropriately to their new milieu such that they fail to migrate or appear to migrate randomly. When trunk neural folds are grafted heterotopically into the head, trunk neural crest cells migrate in a highly disorganized fashion and fail to follow normal cranial neural crest pathways. Importantly, we find incorporation of some trunk cells into branchial arch cartilage despite the random nature of their migration. This is the first demonstration that trunk neural crest cells can form cartilage when transplanted to the head. Our results indicate that, although cranial and trunk neural crest cells have inherent differences in ability to recognize migratory pathways, trunk neural crest can differentiate into cranial cartilage when given proper instructive cues.

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