Arl13b-regulated Cilia Activities Are Essential for Polarized Radial Glial Scaffold Formation

Nat Neurosci. 2013 Aug;16(8):1000-7. doi: 10.1038/nn.3451. Epub 2013 Jun 30.

Abstract

The construction of cerebral cortex begins with the formation of radial glia. Once formed, polarized radial glial cells divide either symmetrically or asymmetrically to balance appropriate production of progenitor cells and neurons. Following birth, neurons use the processes of radial glia as scaffolding for oriented migration. Radial glia therefore provide an instructive structural matrix to coordinate the generation and placement of distinct groups of cortical neurons in the developing cerebral cortex. We found that Arl13b, a cilia-enriched small GTPase that is mutated in Joubert syndrome, was critical for the initial formation of the polarized radial progenitor scaffold. Using developmental stage-specific deletion of Arl13b in mouse cortical progenitors, we found that early neuroepithelial deletion of ciliary Arl13b led to a reversal of the apical-basal polarity of radial progenitors and aberrant neuronal placement. Arl13b modulated ciliary signaling necessary for radial glial polarity. Our findings indicate that Arl13b signaling in primary cilia is crucial for the initial formation of a polarized radial glial scaffold and suggest that disruption of this process may contribute to aberrant neurodevelopment and brain abnormalities in Joubert syndrome-related ciliopathies.

Publication types

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

MeSH terms

  • ADP-Ribosylation Factors / deficiency
  • ADP-Ribosylation Factors / genetics
  • ADP-Ribosylation Factors / physiology*
  • Abnormalities, Multiple
  • Animals
  • Axoneme / ultrastructure
  • Cell Division
  • Cell Polarity
  • Cerebellar Diseases / enzymology
  • Cerebellar Diseases / genetics
  • Cerebellar Diseases / pathology
  • Cerebellum / abnormalities
  • Cerebral Cortex / abnormalities
  • Cerebral Cortex / embryology
  • Cerebral Cortex / growth & development
  • Cerebral Ventricles / abnormalities
  • Cilia / enzymology*
  • Cilia / physiology
  • Epithelium / ultrastructure
  • Eye Abnormalities / enzymology
  • Eye Abnormalities / genetics
  • Eye Abnormalities / pathology
  • Humans
  • Kidney Diseases, Cystic / enzymology
  • Kidney Diseases, Cystic / genetics
  • Kidney Diseases, Cystic / pathology
  • Mice
  • Mice, Inbred C3H
  • Mice, Knockout
  • Nerve Tissue Proteins / deficiency
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / physiology*
  • Neural Stem Cells / physiology
  • Neural Stem Cells / ultrastructure
  • Neurogenesis / genetics
  • Neurogenesis / physiology*
  • Neuroglia / physiology
  • Neuroglia / ultrastructure*
  • Retina / abnormalities
  • Retina / enzymology
  • Retina / pathology
  • Telencephalon / embryology
  • Telencephalon / ultrastructure

Substances

  • Arl13b protein, mouse
  • Nerve Tissue Proteins
  • ADP-Ribosylation Factors
  • Arl13b protein, human

Supplementary concepts

  • Agenesis of Cerebellar Vermis