Rac1 deficiency in the forebrain results in neural progenitor reduction and microcephaly

Dev Biol. 2009 Jan 1;325(1):162-70. doi: 10.1016/j.ydbio.2008.10.023. Epub 2008 Oct 31.


The Rho family of small GTPases has been implicated in many neurological disorders including mental retardation, but whether they are involved in primary microcephaly (microcephalia vera) is unknown. Here, we examine the role of Rac1 in mammalian neural progenitors and forebrain development by a conditional gene-targeting strategy using the Foxg1-Cre line to delete floxed-Rac1 alleles in the telencephalic ventricular zone (VZ) of mouse embryos. We found that Rac1 deletion in the telencephalic VZ progenitors resulted in reduced sizes of both the striatum and cerebral cortex. Analyses further indicated that this abnormality was caused by accelerated cell-cycle exit and increased apoptosis during early corticogenesis (approximately E14.5), leading to a decrease of the neural progenitor pool in mid-to-late telencephalic development (E16.5 to E18.5). Moreover, the formation of patch-matrix compartments in the striatum was impaired by Rac1-deficiency. Together, these results suggest that Rac1 regulates self-renewal, survival, and differentiation of telencephalic neural progenitors, and that dysfunctions of Rac1 may lead to primary microcephaly.

MeSH terms

  • Animals
  • Apoptosis
  • Cell Cycle
  • Cell Differentiation
  • Embryonic Development
  • Gene Deletion
  • Mice
  • Microcephaly / enzymology*
  • Microcephaly / pathology
  • Models, Biological
  • Neostriatum / enzymology
  • Neostriatum / pathology
  • Neurons / enzymology*
  • Neurons / pathology*
  • Neuropeptides / deficiency*
  • Neuropeptides / metabolism
  • Prosencephalon / enzymology*
  • Prosencephalon / pathology*
  • Stem Cells / enzymology*
  • Stem Cells / pathology
  • Telencephalon / enzymology
  • Telencephalon / pathology
  • rac GTP-Binding Proteins / deficiency*
  • rac GTP-Binding Proteins / metabolism
  • rac1 GTP-Binding Protein


  • Neuropeptides
  • Rac1 protein, mouse
  • rac GTP-Binding Proteins
  • rac1 GTP-Binding Protein