Primary cilia and Gli3 activity regulate cerebral cortical size. Academic Article uri icon

Overview

MeSH

  • Animals
  • Cilia
  • Female
  • Male
  • Mice
  • Mice, Transgenic
  • Nervous System Malformations
  • Neurogenesis
  • Organ Size

MeSH Major

  • Cerebral Cortex
  • Kruppel-Like Transcription Factors
  • Nerve Tissue Proteins

abstract

  • During neural development patterning, neurogenesis, and overall growth are highly regulated and coordinated between different brain regions. Here, we show that primary cilia and the regulation of Gli activity are necessary for the normal expansion of the cerebral cortex. We show that loss of Kif3a, an important functional component of primary cilia, leads to the degeneration of primary cilia, marked overgrowth of the cortex, and altered cell cycle kinetics within cortical progenitors. The G1 phase of the cell cycle is shortened through a mechanism likely involving reduced Gli3 activity and a resulting increase in expression of cyclin D1 and Fgf15. The defects in Gli3 activity alone are sufficient to accelerate cell cycle kinetics and cause the molecular changes seen in brains that lack cilia. Finally, we show that levels of full-length and repressor Gli3 proteins are tightly regulated during normal development and correlate with changes in expression of two known Shh-target genes, CyclinD1 and Fgf15, and with the normal lengthening of the cell cycle during corticogenesis. These data suggest that Gli3 activity is regulated through the primary cilium to control cell cycle length in the cortex and thus determine cortical size. Copyright © 2011 Wiley Periodicals, Inc.

publication date

  • September 2012

has subject area

  • Animals
  • Cerebral Cortex
  • Cilia
  • Female
  • Kruppel-Like Transcription Factors
  • Male
  • Mice
  • Mice, Transgenic
  • Nerve Tissue Proteins
  • Nervous System Malformations
  • Neurogenesis
  • Organ Size

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3350755

Digital Object Identifier (DOI)

  • 10.1002/dneu.20985

PubMed ID

  • 21976438

Additional Document Info

start page

  • 1196

end page

  • 1212

volume

  • 72

number

  • 9