Rest regulates non-cell-autonomous neuronal differentiation and maturation of neural progenitor cells via secretogranin II

Hyung Joon Kim, Ahmet M. Denli, Rebecca Wright, Tithi D. Baul, Gregory D. Clemenson, Ari S. Morcos, Chunmei Zhao, Simon T. Schafer, Fred H. Gage, Mohamedi N. Kagalwala

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

RE-1 silencing transcription factor (REST), a master negative regulator of neuronal differentiation, controls neurogenesis by preventing the differentiation of neural stem cells. Here we focused on the role of REST in the early steps of differentiation and maturation of adult hippocampal progenitors (AHPs). REST knockdown promoted differentiation and affected the maturation of rat AHPs. Surprisingly, REST knockdown cells enhanced the differentiation of neighboring wild-type AHPs, suggesting that REST may play a non-cellautonomous role. Gene expression analysis identified Secretogranin II (Scg2) as the major secreted REST target responsible for the non-cell-autonomous phenotype. Loss-of-function of Scg2 inhibited differentiation in vitro, and exogenous SCG2 partially rescued this phenotype. Knockdown of REST in neural progenitors in mice led to precocious maturation into neurons at the expense of mushroom spines in vivo. In summary, we found that, in addition to its cell-autonomous function, REST regulates differentiation and maturation of AHPs non-cell-autonomously via SCG2.

Original languageEnglish (US)
Pages (from-to)14872-14884
Number of pages13
JournalJournal of Neuroscience
Volume35
Issue number44
DOIs
StatePublished - Nov 4 2015

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Keywords

  • Adult neurogenesis
  • Microfludics
  • Neurosecretory
  • REST/NRSF
  • SCG2
  • Stem cells

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Kim, H. J., Denli, A. M., Wright, R., Baul, T. D., Clemenson, G. D., Morcos, A. S., Zhao, C., Schafer, S. T., Gage, F. H., & Kagalwala, M. N. (2015). Rest regulates non-cell-autonomous neuronal differentiation and maturation of neural progenitor cells via secretogranin II. Journal of Neuroscience, 35(44), 14872-14884. https://doi.org/10.1523/JNEUROSCI.4286-14.2015