Published in

Nature Research, Nature Neuroscience, 8(16), p. 1000-1007, 2013

DOI: 10.1038/nn.3451

Links

Tools

Export citation

Search in Google Scholar

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

This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

Full text: Download

Green circle
Preprint: archiving allowed
Orange circle
Postprint: archiving restricted
Red circle
Published version: archiving forbidden
Data provided by SHERPA/RoMEO

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. Upon birth, neurons use the processes of radial glia as scaffolding for oriented migration. Radial glia thus provide an instructive structural matrix to coordinate the generation and placement of distinct groups of cortical neurons in the developing cerebral cortex. Here we show that Arl13b, a cilia-specific small GTPase mutated in Joubert syndrome patients, is critical for the initial formation of the polarized radial progenitor scaffold. Through developmental stage-specific deletion of Arl13b in mouse cortical progenitors, we found that early neuroepithelial deletion of ciliary Arl13b leads to a reversal in the apical-basal polarity of radial progenitors and aberrant neuronal placement. Arl13b modulates ciliary signaling necessary for radial glial polarity. Our findings demonstrate that Arl13b signaling in primary cilia is important 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.