Trnp1 regulates expansion and folding of the mammalian cerebral cortex by control of radial glial fate

Cell. 2013 Apr 25;153(3):535-49. doi: 10.1016/j.cell.2013.03.027.

Abstract

Evolution of the mammalian brain encompassed a remarkable increase in size of the cerebral cortex, which includes tangential and radial expansion. However, the mechanisms underlying these key features are still largely unknown. Here, we identified the DNA-associated protein Trnp1 as a regulator of cerebral cortex expansion in both of these dimensions. Gain- and loss-of-function experiments in the mouse cerebral cortex in vivo demonstrate that high Trnp1 levels promote neural stem cell self-renewal and tangential expansion. In contrast, lower levels promote radial expansion, with a potent increase of the number of intermediate progenitors and basal radial glial cells leading to folding of the otherwise smooth murine cerebral cortex. Remarkably, TRNP1 expression levels exhibit regional differences in the cerebral cortex of human fetuses, anticipating radial or tangential expansion. Thus, the dynamic regulation of Trnp1 is critical to control tangential and radial expansion of the cerebral cortex in mammals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cerebral Cortex / cytology
  • Cerebral Cortex / growth & development*
  • DNA-Binding Proteins
  • Embryo, Mammalian / metabolism
  • Gene Knockdown Techniques
  • Humans
  • Mice
  • Molecular Sequence Data
  • Neural Stem Cells / metabolism
  • Neuroglia / metabolism
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Transcriptional Activation

Substances

  • DNA-Binding Proteins
  • Nuclear Proteins
  • Trnp1 protein, human
  • Trnp1 protein, mouse

Associated data

  • GEO/GSE40582