RTP801/REDD1 regulates the timing of cortical neurogenesis and neuron migration

J Neurosci. 2011 Mar 2;31(9):3186-96. doi: 10.1523/JNEUROSCI.4011-10.2011.

Abstract

The generation, differentiation, and migration of newborn neurons are critical features of normal brain development that are subject to both extracellular and intracellular regulation. However, the means of such control are only partially understood. Here, we show that expression of RTP801/REDD1, an inhibitor of mTOR (mammalian target of rapamycin) activation, is regulated during neuronal differentiation and that RTP801 functions to influence the timing of both neurogenesis and neuron migration. RTP801 levels are high in embryonic cortical neuroprogenitors, diminished in newborn neurons, and low in mature neurons. Knockdown of RTP801 in vitro and in vivo accelerates cell cycle exit by neuroprogenitors and their differentiation into neurons. It also disrupts migration of rat newborn neurons to the cortical plate and results in the ectopic localization of mature neurons. On the other hand, RTP801 overexpression delays neuronal differentiation. These findings suggest that endogenous RTP801 plays an essential role in temporal control of cortical development and in cortical patterning.

Publication types

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

MeSH terms

  • Animals
  • Body Patterning / genetics
  • Body Patterning / physiology
  • Cell Differentiation / genetics
  • Cell Differentiation / physiology
  • Cell Movement / genetics
  • Cell Movement / physiology*
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Cerebral Cortex / physiology*
  • Gene Knockdown Techniques
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Neurogenesis / genetics
  • Neurogenesis / physiology*
  • Neurons / cytology*
  • Neurons / physiology*
  • PC12 Cells
  • Rats
  • Repressor Proteins / antagonists & inhibitors
  • Repressor Proteins / genetics
  • Repressor Proteins / physiology*
  • Stem Cells / cytology
  • Stem Cells / physiology
  • Time Factors
  • Transcription Factors

Substances

  • Ddit4 protein, rat
  • Repressor Proteins
  • Transcription Factors