BDNF activates an NFI-dependent neurodevelopmental timing program by sequestering NFATc4

Mol Biol Cell. 2018 Apr 15;29(8):975-987. doi: 10.1091/mbc.E16-08-0595. Epub 2018 Mar 30.

Abstract

We show that BDNF regulates the timing of neurodevelopment via a novel mechanism of extranuclear sequestration of NFATc4 in Golgi. This leads to accelerated derepression of an NFI temporal occupancy gene program in cerebellar granule cells that includes Bdnf itself, revealing an autoregulatory loop within the program driven by BDNF and NFATc4.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Cell Differentiation / genetics
  • Cells, Cultured
  • Cerebellum / growth & development*
  • Gene Expression Regulation, Developmental*
  • HEK293 Cells
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NFATC Transcription Factors / genetics
  • NFATC Transcription Factors / metabolism*
  • NFI Transcription Factors / genetics
  • NFI Transcription Factors / metabolism*
  • Neurons / metabolism

Substances

  • Brain-Derived Neurotrophic Factor
  • NFATC Transcription Factors
  • NFI Transcription Factors
  • Nfatc4 protein, mouse