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Dev Cell. 2015 Sep 14;34(5):544-54. doi: 10.1016/j.devcel.2015.06.024. Epub 2015 Aug 6.

Axud1 Integrates Wnt Signaling and Transcriptional Inputs to Drive Neural Crest Formation.

Author information

  • 1Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
  • 2Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA. Electronic address: mbronner@caltech.edu.

Abstract

Neural crest cells are induced at the neural plate border by the combined action of transcription factors and signaling molecules. Here, we show that Axud1, a downstream effector of Wnt signaling, represents a critical missing link that integrates signaling and transcriptional cues to mediate neural crest formation. Axud1 is a transcription factor expressed in neural crest progenitors in a Wnt1/β-catenin-dependent manner. Axud1 loss leads to downregulation of multiple genes involved in neural crest specification, similar to the effects of Wnt1 knockdown. Importantly, Axud1 is sufficient to rescue neural crest formation after disruption of Wnt signaling. Furthermore, it physically interacts with neural plate border genes Pax7 and Msx1 in vivo to directly activate transcription of stem cell factor FoxD3, initiating the neural crest program. Thus, Axud1 integrates Wnt signaling with transcriptional inputs to endow the neural crest with its unique molecular signature.

PMID:
26256212
PMCID:
PMC4573882
DOI:
10.1016/j.devcel.2015.06.024
[PubMed - indexed for MEDLINE]
Free PMC Article
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