The adenomatous polyposis coli protein is an essential regulator of radial glial polarity and construction of the cerebral cortex

Neuron. 2009 Jan 15;61(1):42-56. doi: 10.1016/j.neuron.2008.10.053.


Radial glia are highly polarized cells that serve as neuronal progenitors and as scaffolds for neuronal migration during construction of the cerebral cortex. How radial glial cells establish and maintain their morphological polarity is unknown. Using conditional gene targeting in mice, we demonstrate that adenomatous polyposis coli (APC) serves an essential function in the maintenance of polarized radial glial scaffold during brain development. In the absence of APC, radial glial cells lose their polarity and responsiveness to the extracellular polarity maintenance cues, such as neuregulin-1. Elimination of APC further leads to marked instability of the radial glial microtubule cytoskeleton. The resultant changes in radial glial function and loss of APC in radial glial progeny lead to defective generation and migration of cortical neurons, severely disrupted cortical layer formation, and aberrant axonal tract development. Thus, APC is an essential regulator of radial glial polarity and is critical for the construction of cerebral cortex in mammals.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenomatous Polyposis Coli Protein / genetics
  • Adenomatous Polyposis Coli Protein / metabolism*
  • Animals
  • Cell Movement / physiology
  • Cell Polarity*
  • Cell Proliferation
  • Cerebral Cortex* / cytology
  • Cerebral Cortex* / embryology
  • Intermediate Filament Proteins / genetics
  • Intermediate Filament Proteins / metabolism
  • Mice
  • Mice, Knockout
  • Microtubules / metabolism
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Nestin
  • Neuregulin-1 / genetics
  • Neuregulin-1 / metabolism
  • Neurogenesis / physiology
  • Neuroglia* / cytology
  • Neuroglia* / physiology
  • beta Catenin / genetics
  • beta Catenin / metabolism


  • Adenomatous Polyposis Coli Protein
  • Intermediate Filament Proteins
  • Nerve Tissue Proteins
  • Nes protein, mouse
  • Nestin
  • Neuregulin-1
  • beta Catenin