Early But Not Delayed Optogenetic RAF Activation Promotes Astrocytogenesis in Mouse Neural Progenitors

Yixun Su, Xiaomin Huang, Zhangsen Huang, Taida Huang, Tao Li, Huaxun Fan, Kai Zhang, Chenju Yi

Research output: Contribution to journalArticle

Abstract

The RAS/RAF/MEK/ERK pathway promotes gliogenesis but the kinetic role of RAF1, a key RAF kinase, in the induction of astrocytogenesis remains to be elucidated. To address this challenge, we determine the temporal functional outcome of RAF1 during mouse neural progenitor cell differentiation using an optogenetic RAF1 system (OptoRAF1). OptoRAF1 allows for reversible activation of the RAF/MEK/ERK pathway via plasma membrane recruitment of RAF1 based on blue light-sensitive protein dimerizer CRY2/CIB1. We found that early light-induced OptoRAF1 activation in neural progenitor cells promotes cell proliferation and increased expression of glial markers and glia-enriched genes. However, delayed OptoRAF1 activation in differentiated neural progenitor had little effect on glia marker expression, suggesting that RAF1 is required to promote astrocytogenesis only within a short time window. In addition, activation of OptoRAF1 did not have a significant effect on neurogenesis, but was able to promote neuronal neurite growth.

Original languageEnglish (US)
Pages (from-to)4358-4368
Number of pages11
JournalJournal of Molecular Biology
Volume432
Issue number16
DOIs
StatePublished - Jul 24 2020

Keywords

  • OptoRAF1
  • Optogenetic
  • RAF1
  • astrocytogenesis
  • neural progenitor

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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