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Author Notes:

Correspondence to: E. S. Anton, UNC Neuroscience Center and the Department of Cell and Molecular Physiology, The University of North Carolina School of Medicine, Chapel Hill, NC 27599, anton@med.unc.edu, PHONE: 919-843-6114, FAX: 919-966-1844.

Holden Higginbotham and Jiami Guo contributed equally.

E.A., H.H., J.G., Y.Y., and T.C. designed the experiments and supervised the project.

H.H., J.G., Y.Y., N.L.U., C.S., J.L., and N.V. conducted the experiments and analyzed the data.

E.A., H.H., J.G., and T.C. wrote the manuscript.

We thank A- S. Lamantia, L. Pevny, M. Deshmukh and W. Snider for helpful comments and C. T. Strauss for editing.

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Research Funding:

This research was supported by NIH grants MH060929 to E.S.A. and NS056380 to T.C., a NARSAD Young Investigator Award to H.H., a NIH predoctoral training grant to N.L.U. T32GM008490 and by the confocal imaging core of an NINDS institutional center core grant.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Neurosciences
  • Neurosciences & Neurology
  • DEVELOPING CEREBRAL-CORTEX
  • JOUBERT-SYNDROME
  • CEREBROSPINAL-FLUID
  • BASAL PROGENITORS
  • CORTICAL-NEURONS
  • ARL13B
  • DIFFERENTIATION
  • PROTEIN
  • NEUROGENESIS
  • CILIOGENESIS

Arl13b-regulated cilia activities are essential for polarized radial glial scaffold formation

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Journal Title:

Nature Neuroscience

Volume:

Volume 16, Number 8

Publisher:

, Pages 1000-U44

Type of Work:

Article | Post-print: After Peer Review

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.

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