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

• Type of Material: Article
• Authors: Holden Higginbotham, University of North Carolina; Jiami Guo, University of North Carolina; Yukako Yokota, University of North Carolina; Nicole L. Umberger, Emory University; Chen-Ying Su, Emory University; Jingjun Li, University of North Carolina; Nisha Verma, University of North Carolina; Joshua Hirt, University of North Carolina; Vladimir Ghukasyan, University of North Carolina; Tamara Caspary, Emory University; E.S. Anton, University of North Carolina
• Language: English
• Date: 2013-08-01
• Publisher: Nature Publishing Group
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2013 Nature America, Inc. All rights reserved. Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
• Final Published Version (URL): http://dx.doi.org/10.1038/nn.3451
• Title of Journal or Parent Work: Nature Neuroscience
• ISSN: 1097-6256
• Volume: 16
• Issue: 8
• Start Page: 1000
• End Page: U44
• Grant/Funding Information: 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: Neurosciences; DEVELOPING CEREBRAL-CORTEX; Neurosciences & Neurology; JOUBERT-SYNDROME; ARL13B; NEUROGENESIS; PROTEIN; Life Sciences & Biomedicine; CILIOGENESIS; DIFFERENTIATION; CORTICAL-NEURONS; BASAL PROGENITORS; CEREBROSPINAL-FLUID; Science & Technology
• Research Categories: Biology, Genetics; Biology, Neuroscience; Biology, Cell

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.