Document Detail


Loss of RhoA in neural progenitor cells causes the disruption of adherens junctions and hyperproliferation.
MedLine Citation:
PMID:  21502507     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The organization of neural progenitors in the developing mammalian neuroepithelium is marked by cadherin-based adherens junctions. Whereas RhoA, a founding member of the small Rho GTPase family, has been shown to play important roles in epithelial adherens junctions, its physiological roles in neural development remain uncertain due to the lack of specific loss-of-function studies. Here, we show that RhoA protein accumulates at adherens junctions in the developing mouse brain and colocalizes to the cadherin-catenin complex. Conditional deletion of RhoA in midbrain and forebrain neural progenitors using Wnt1-Cre and Foxg1-Cre mice, respectively, disrupts apical adherens junctions and causes massive dysplasia of the brain. Furthermore, RhoA-deficient neural progenitor cells exhibit accelerated proliferation, reduction of cell- cycle exit, and increased expression of downstream target genes of the hedgehog pathway. Consequently, both lines of conditional RhoA-deficient embryos exhibit expansion of neural progenitor cells and exencephaly-like protrusions. These results demonstrate a critical role of RhoA in the maintenance of apical adherens junctions and the regulation of neural progenitor proliferation in the developing mammalian brain.
Authors:
Kei-ichi Katayama; Jaime Melendez; Jessica M Baumann; Jennifer R Leslie; Bharesh K Chauhan; Niza Nemkul; Richard A Lang; Chia-Yi Kuan; Yi Zheng; Yutaka Yoshida
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-04-18
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  108     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-05-04     Completed Date:  2011-07-15     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  7607-12     Citation Subset:  IM    
Affiliation:
Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
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MeSH Terms
Descriptor/Qualifier:
Adherens Junctions / metabolism*
Animals
Brain / embryology*
Bromodeoxyuridine
Cell Proliferation*
Immunohistochemistry
Immunoprecipitation
In Situ Hybridization
In Situ Nick-End Labeling
Indoles
Mice
Mice, Mutant Strains
Microscopy, Confocal
Neural Stem Cells / metabolism*
Reverse Transcriptase Polymerase Chain Reaction
rhoA GTP-Binding Protein / deficiency*,  metabolism
Chemical
Reg. No./Substance:
0/Indoles; 47165-04-8/DAPI; 59-14-3/Bromodeoxyuridine; EC 3.6.5.2/rhoA GTP-Binding Protein
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