Specification of Sensory Neuron Cell Fate from the Neural Crest

22q11.2 Deletion Syndrome (22q11DS) is a neurodevelopmental disorder associated with cranial nerve anomalies and disordered oropharyngeal function including pediatric dysphagia. Using the LgDel 22q11DS mouse model, we asked whether sensory neuron differentiation in the trigeminal ganglion (CNgV) , which is essential for normal orofacial function, is disrupted. We did not detect changes in cranial placode cell translocation or neural crest migration at early stages of LgDel CNgV development. As the ganglion coalesces, however, proportions of placode-derived LgDel CNgV cells increase relative to neural crest cells. In addition, local aggregation of placode-derived cells increases and aggregation of neural crest-derived cells decreases in LgDel CNgV. This change in cell-cell relationships was accompanied by altered proliferation of placode-derived cells at E9.5, and premature neurogenesis from neural crest-derived precursors, reflected by increased frequency of asymmetric neurogenic divisions for neural crest-derived precursors by E10.5. These early differences in LgDel CNgV genesis prefigure changes in sensory neuron differentiation and gene expression by P8, when early signs of cranial nerve dysfunction associated with pediatric dysphagia are observed in LgDel mice. Apparently, 22q11 deletion destabilizes CNgV sensory neuron genesis and differentiation by increasing variability in cell-cell interaction, proliferation, and sensory neuron differentiation. This early developmental divergence and its consequences may contribute to oropharyngeal dysfunction including suckling, feeding and swallowing disruptions at birth and additional orofacial sensory/motor deficits throughout life.

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

Scientific Reports ◽

10.1038/srep23208 ◽

2016 ◽

Vol 6 (1) ◽

Cited By ~ 51

Author(s):

Christopher J. Hindley ◽

Alexandra Larisa Condurat ◽

Vishal Menon ◽

Ria Thomas ◽

Luis M. Azmitia ◽

...

Keyword(s):

Neural Crest ◽

Cell Fate ◽

Hippo Pathway ◽

Neural Crest Cell ◽

And Migration ◽

The Hippo Pathway ◽

Crest Cell

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Cell Fate and Gene Expression in the Developing Neural Crest

Neural Development and Regeneration ◽

10.1007/978-3-642-73148-8_17 ◽

1988 ◽

pp. 187-198 ◽

Cited By ~ 4

Author(s):

D. J. Anderson

Keyword(s):

Gene Expression ◽

Neural Crest ◽

Cell Fate

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Basic FGF and TGF-beta 1 influence commitment to melanogenesis in neural crest-derived cells of avian embryos

Development ◽

10.1242/dev.111.2.635 ◽

1991 ◽

Vol 111 (2) ◽

pp. 635-645 ◽

Cited By ~ 5

Author(s):

K.M. Stocker ◽

L. Sherman ◽

S. Rees ◽

G. Ciment

Keyword(s):

Growth Factors ◽

Growth Factor ◽

Neural Crest ◽

Cell Fate ◽

Transforming Growth Factor Beta ◽

Culture Medium ◽

Transforming Growth Factor ◽

Neutralizing Antibody ◽

Pigment Cells ◽

Tgf Beta

In previous studies, we showed that neural crest (NC)-derived cells from embryonic quail dorsal root ganglia (DRG) and peripheral nerve (PN), which do not normally give rise to melanocytes, become committed to melanogenesis following treatment in culture with the phorbol ester drug 12-O-tetradecanoyl phorbol-13-acetate (TPA). These and other observations support the notion that melanocytes and Schwann cells are derived from a common bipotent intermediate in the neural crest lineage—the melanocyte/Schwann cell progenitor. In this study, we test the possibility that peptide growth factors found in the embryonic environment might act similarly to TPA to influence the fates of these cells. DRG and PN explants were cultured in medium supplemented with a variety of growth factors, and then the cultures were examined for the presence of pigment cells. We found that basic fibroblast growth factor (bFGF), but not various other growth factors, induced pigmentation in about 20% of these cultures. When low concentrations of TPA were included in the culture medium, bFGF augmented the TPA-induced pigmentation, significantly increasing the proportion of pigmented cultures. These effects of bFGF were age-dependent, and could be blocked by addition of a bFGF-neutralizing antibody to the culture medium. In contrast to these stimulatory effects of bFGF, transforming growth factor-beta 1 (TGF-beta 1) was found to inhibit the TPA- or bFGF-induced pigmentation of DRG cultures. These data suggest, therefore, that at least some NC-derived cells are responsive to bFGF and TGF-beta 1, and that these growth factors may play an important role in the control of NC cell fate.

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nacre encodes a zebrafish microphthalmia-related protein that regulates neural-crest-derived pigment cell fate

Development ◽

10.1242/dev.126.17.3757 ◽

1999 ◽

Vol 126 (17) ◽

pp. 3757-3767 ◽

Cited By ~ 40

Author(s):

J.A. Lister ◽

C.P. Robertson ◽

T. Lepage ◽

S.L. Johnson ◽

D.W. Raible

Keyword(s):

Transcription Factor ◽

Retinal Pigment Epithelium ◽

Neural Crest ◽

Cell Fate ◽

Pigment Cell ◽

Pigment Epithelium ◽

Retinal Pigment ◽

Pigment Cells ◽

Evolutionary Divergence ◽

Wild Type

We report the isolation and identification of a new mutation affecting pigment cell fate in the zebrafish neural crest. Homozygous nacre (nac(w2)) mutants lack melanophores throughout development but have increased numbers of iridophores. The non-crest-derived retinal pigment epithelium is normal, suggesting that the mutation does not affect pigment synthesis per se. Expression of early melanoblast markers is absent in nacre mutants and transplant experiments suggested a cell-autonomous function in melanophores. We show that nac(w2) is a mutation in a zebrafish gene encoding a basic helix-loop-helix/leucine zipper transcription factor related to microphthalmia (Mitf), a gene known to be required for development of eye and crest pigment cells in the mouse. Transient expression of the wild-type nacre gene restored melanophore development in nacre(−/−) embryos. Furthermore, misexpression of nacre induced the formation of ectopic melanized cells and caused defects in eye development in wild-type and mutant embryos. These results demonstrate that melanophore development in fish and mammals shares a dependence on the nacre/Mitf transcription factor, but that proper development of the retinal pigment epithelium in the fish is not nacre-dependent, suggesting an evolutionary divergence in the function of this gene.

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LKB1 specifies neural crest cell fates through pyruvate-alanine cycling

Science Advances ◽

10.1126/sciadv.aau5106 ◽

2019 ◽

Vol 5 (7) ◽

pp. eaau5106 ◽

Cited By ~ 2

Author(s):

Anca G. Radu ◽

Sakina Torch ◽

Florence Fauvelle ◽

Karin Pernet-Gallay ◽

Anthony Lucas ◽

...

Keyword(s):

Neural Crest ◽

Cell Fate ◽

Neural Crest Cell ◽

Dependent Manner ◽

Cell Fates ◽

Neural Crest Stem Cells ◽

Metabolomic Profiling ◽

Intestinal Pseudo Obstruction ◽

Migratory Cells ◽

Hind Limb Paralysis

Metabolic processes underlying the development of the neural crest, an embryonic population of multipotent migratory cells, are poorly understood. Here, we report that conditional ablation of the Lkb1 tumor suppressor kinase in mouse neural crest stem cells led to intestinal pseudo-obstruction and hind limb paralysis. This phenotype originated from a postnatal degeneration of the enteric nervous ganglia and from a defective differentiation of Schwann cells. Metabolomic profiling revealed that pyruvate-alanine conversion is enhanced in the absence of Lkb1. Mechanistically, inhibition of alanine transaminases restored glial differentiation in an mTOR-dependent manner, while increased alanine level directly inhibited the glial commitment of neural crest cells. Treatment with the metabolic modulator AICAR suppressed mTOR signaling and prevented Schwann cell and enteric defects of Lkb1 mutant mice. These data uncover a link between pyruvate-alanine cycling and the specification of glial cell fate with potential implications in the understanding of the molecular pathogenesis of neural crest diseases.

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