Neogenin promotes BMP2 activation of YAP and smad1 and enhances astrocytic differentiation in developing mouse neocortex

Zhihui Huang, Dong Sun, Jin Xia Hu, Fulei Tang, Dae Hoon Lee, Ying Wang, Guoqing Hu, Xiao Juan Zhu, Jiliang Zhou, Wencheng Xiong

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Neogenin, a DCC (deleted in colorectal cancer) family receptor, is highly expressed in neural stem cells (NSCs). However, its function in NSCs remains to be explored. Here we provide in vitro and in vivo evidence for neogenin's function in NSCs to promote neocortical astrogliogenesis, but not self-renewal or neural differentiation. Mechanistically, neogenin in neocortical NSCs was required for BMP2 activation of YAP (yes associated protein). The active/nuclear YAP stabilized phospho-Smad1/5/8 and was necessary for BMP2 induction of astrocytic differentiation. Deletion of yap in mouse neocortical NSCs caused a similar deficit in neocortical astrogliogenesis as that in neogenin mutant mice. Expression of YAP in neogenin mutant NSCs diminished the astrocytic differentiation deficit in response to BMP2. Together, these results reveal an unrecognized function of neogenin in increasing neocortical astrogliogenesis, and identify a pathway of BMP2-neogenin-YAP-Smad1 for astrocytic differentiation in developing mouse neocortex.

Original languageEnglish (US)
Pages (from-to)5833-5849
Number of pages17
JournalJournal of Neuroscience
Volume36
Issue number21
DOIs
StatePublished - May 25 2016

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Keywords

  • Astrocytes
  • BMP2
  • Differentiation
  • Neogenin
  • YAP

ASJC Scopus subject areas

  • Neuroscience(all)

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