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Type: Journal article
Title: The ubiquitin ligase Nedd4 regulates craniofacial development by promoting cranial neural crest cell survival and stem-cell like properties
Author: Wiszniak, S.
Kabbara, S.
Lumb, R.
Scherer, M.
Secker, G.
Harvey, N.
Kumar, S.
Schwarz, Q.
Citation: Developmental Biology, 2013; 383(2):186-200
Publisher: Academic Press Inc Elsevier Science
Issue Date: 2013
ISSN: 0012-1606
Statement of
Sophie Wiszniak, Samuela Kabbara, Rachael Lumb, Michaela Scherer, Genevieve Secker, Natasha Harvey, Sharad Kumar, Quenten Schwarz
Abstract: The integration of multiple morphogenic signalling pathways and transcription factor networks is essential to mediate neural crest (NC) cell induction, delamination, survival, stem-cell properties, fate choice and differentiation. Although the transcriptional control of NC development is well documented in mammals, the role of post-transcriptional modifications, and in particular ubiquitination, has not been explored. Here we report an essential role for the ubiquitin ligase Nedd4 in cranial NC cell development. Our analysis of Nedd4(-/-) embryos identified profound deficiency of cranial NC cells in the absence of structural defects in the neural tube. Nedd4 is expressed in migrating cranial NC cells and was found to positively regulate expression of the NC transcription factors Sox9, Sox10 and FoxD3. We found that in the absence of these factors, a subset of cranial NC cells undergo apoptosis. In accordance with a lack of cranial NC cells, Nedd4(-/-) embryos have deficiency of the trigeminal ganglia, NC derived bone and malformation of the craniofacial skeleton. Our analyses therefore uncover an essential role for Nedd4 in a subset of cranial NC cells and highlight E3 ubiquitin ligases as a likely point of convergence for multiple NC signalling pathways and transcription factor networks.
Keywords: Neural crest cell
Ubiquitin ligase
Stem-cell maintenance
Rights: Copyright © 2013 Elsevier Inc.
DOI: 10.1016/j.ydbio.2013.09.024
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