The ubiquitin ligase Nedd4 regulates craniofacial development by promoting cranial neural crest cell survival and

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An Explant Assay for Assessing Cellular Behavior of the Cranial Mesenchyme
07:45

An Explant Assay for Assessing Cellular Behavior of the Cranial Mesenchyme

Published on: January 20, 2013

Sophie Wiszniak1, Samuela Kabbara, Rachael Lumb

  • 1Centre for Cancer Biology, SA Pathology, Frome Road, Adelaide, 5000, Australia.

Developmental Biology
|October 2, 2013
PubMed

Insights

The ubiquitin ligase Nedd4 is crucial for cranial neural crest (NC) cell development. Its absence leads to a severe deficiency in NC cells, impacting craniofacial development and survival.

Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Genetics

Background:

  • Neural crest (NC) cell development involves complex signaling and transcription factor networks.
  • Post-transcriptional modifications, particularly ubiquitination, remain understudied in NC development.
  • The role of E3 ubiquitin ligases in NC cell fate and survival is largely unknown.

Purpose of the Study:

  • To investigate the role of the ubiquitin ligase Nedd4 in cranial neural crest (NC) cell development.
  • To determine the impact of Nedd4 deficiency on NC cell survival, transcription factor expression, and craniofacial formation.

Main Methods:

  • Analysis of Nedd4 knockout (Nedd4(-/-)) mouse embryos.
  • Immunohistochemistry to assess Nedd4 expression in migrating NC cells.
  • Quantitative analysis of NC-derived cell populations and craniofacial structures.
  • Examination of key NC transcription factor (Sox9, Sox10, FoxD3) expression levels.

Main Results:

  • Nedd4(-/-) embryos exhibit a significant deficiency in cranial NC cells without neural tube structural defects.
  • Nedd4 is expressed in migrating cranial NC cells and positively regulates Sox9, Sox10, and FoxD3 expression.
  • Loss of Nedd4 leads to apoptosis in a subset of cranial NC cells.
  • Nedd4 deficiency results in underdeveloped trigeminal ganglia, reduced NC-derived bone, and craniofacial malformations.

Conclusions:

  • Nedd4 plays an essential role in the survival and development of a subset of cranial NC cells.
  • Nedd4 regulates key transcription factors necessary for cranial NC cell development.
  • E3 ubiquitin ligases represent a critical convergence point for NC signaling and transcription factor networks.
Keywords:
EctomesenchymeNedd4Neural crest cellNeuroglialStem-cell maintenanceUbiquitin ligase

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