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

• 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
• Journal Title: Nature Neuroscience
• Volume: Volume 16, Number 8
• Publisher: Nature Publishing Group | 2013-08-01, Pages 1000-U44
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1038/nn.3451
• Subjects: Biology, Cell; Biology, Genetics; Biology, Neuroscience
• 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

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.