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Nature Neuroscience
Article
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Nature Neuroscience
Article . 2013 . Peer-reviewed
License: Springer TDM
Data sources: Crossref
UNC Dataverse
Article . 2013
Data sources: Datacite
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Arl13b-regulated cilia activities are essential for polarized radial glial scaffold formation

Authors: Holden, Higginbotham; Jiami, Guo; Yukako, Yokota; Nicole L, Umberger; Chen-Ying, Su; Jingjun, Li; Nisha, Verma; +4 Authors

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

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.

Keywords

Cerebral Cortex, Mice, Knockout, Mice, Inbred C3H, Axoneme, ADP-Ribosylation Factors, Cell Polarity, Nerve Tissue Proteins, Kidney Diseases, Cystic, Epithelium, Cerebral Ventricles, Mice, Neural Stem Cells, Cerebellar Diseases, Cerebellum, Animals, Humans, Abnormalities, Multiple, Cilia, Eye Abnormalities, Cell Division

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    selected citations
    These citations are derived from selected sources.
    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    189
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 1%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Top 10%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 1%
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
189
Top 1%
Top 10%
Top 1%
hybrid