Document Detail


Primary cilia and Gli3 activity regulate cerebral cortical size.
MedLine Citation:
PMID:  21976438     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
During neural development patterning, neurogenesis, and overall growth are highly regulated and coordinated between different brain regions. Here, we show that primary cilia and the regulation of Gli activity are necessary for the normal expansion of the cerebral cortex. We show that loss of Kif3a, an important functional component of primary cilia, leads to the degeneration of primary cilia, marked overgrowth of the cortex, and altered cell cycle kinetics within cortical progenitors. The G1 phase of the cell cycle is shortened through a mechanism likely involving reduced Gli3 activity and a resulting increase in expression of cyclin D1 and Fgf15. The defects in Gli3 activity alone are sufficient to accelerate cell cycle kinetics and cause the molecular changes seen in brains that lack cilia. Finally, we show that levels of full-length and repressor Gli3 proteins are tightly regulated during normal development and correlate with changes in expression of two known Shh-target genes, CyclinD1 and Fgf15, and with the normal lengthening of the cell cycle during corticogenesis. These data suggest that Gli3 activity is regulated through the primary cilium to control cell cycle length in the cortex and thus determine cortical size.
Authors:
Sandra L Wilson; John P Wilson; Chengbing Wang; Baolin Wang; Susan K McConnell
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-06-21
Journal Detail:
Title:  Developmental neurobiology     Volume:  72     ISSN:  1932-846X     ISO Abbreviation:  Dev Neurobiol     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-08-13     Completed Date:  2013-06-03     Revised Date:  2013-11-15    
Medline Journal Info:
Nlm Unique ID:  101300215     Medline TA:  Dev Neurobiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1196-212     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Wiley Periodicals, Inc.
Affiliation:
Department of Biology, Stanford University, Stanford, California 94305, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cerebral Cortex / cytology,  growth & development*,  physiopathology
Cilia / physiology
Female
Kruppel-Like Transcription Factors / deficiency,  genetics,  physiology*
Male
Mice
Mice, Transgenic
Nerve Tissue Proteins / deficiency,  genetics,  physiology*
Nervous System Malformations / genetics,  physiopathology
Neurogenesis / physiology
Organ Size / physiology
Grant Support
ID/Acronym/Agency:
CA111673/CA/NCI NIH HHS; GM007276/GM/NIGMS NIH HHS; MH51864/MH/NIMH NIH HHS; R37 MH051864/MH/NIMH NIH HHS; R37 MH051864-17/MH/NIMH NIH HHS
Chemical
Reg. No./Substance:
0/Gli3 protein, mouse; 0/Kruppel-Like Transcription Factors; 0/Nerve Tissue Proteins
Comments/Corrections

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