Document Detail


Shp2 acts downstream of SDF-1alpha/CXCR4 in guiding granule cell migration during cerebellar development.
MedLine Citation:
PMID:  19635473     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Shp2 is a non-receptor protein tyrosine phosphatase containing two Src homology 2 (SH2) domains that is implicated in intracellular signaling events controlling cell proliferation, differentiation and migration. To examine the role of Shp2 in brain development, we created mice with Shp2 selectively deleted in neural stem/progenitor cells. Homozygous mutant mice exhibited early postnatal lethality with defects in neural stem cell self-renewal and neuronal/glial cell fate specification. Here we report a critical role of Shp2 in guiding neuronal cell migration in the cerebellum. In homozygous mutants, we observed reduced and less foliated cerebellum, ectopic presence of external granule cells and mispositioned Purkinje cells, a phenotype very similar to that of mutant mice lacking either SDF-1alpha or CXCR4. Consistently, Shp2-deficient granule cells failed to migrate toward SDF-1alpha in an in vitro cell migration assay, and SDF-1alpha treatment triggered a robust induction of tyrosyl phosphorylation on Shp2. Together, these results suggest that although Shp2 is involved in multiple signaling events during brain development, a prominent role of the phosphatase is to mediate SDF-1alpha/CXCR4 signal in guiding cerebellar granule cell migration.
Authors:
Kazuki Hagihara; Eric E Zhang; Yue-Hai Ke; Guofa Liu; Jan-Jan Liu; Yi Rao; Gen-Sheng Feng
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2009-07-25
Journal Detail:
Title:  Developmental biology     Volume:  334     ISSN:  1095-564X     ISO Abbreviation:  Dev. Biol.     Publication Date:  2009 Oct 
Date Detail:
Created Date:  2009-09-15     Completed Date:  2009-12-29     Revised Date:  2014-09-14    
Medline Journal Info:
Nlm Unique ID:  0372762     Medline TA:  Dev Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  276-84     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Brain / metabolism
Cell Differentiation
Cell Movement / physiology*
Cerebellum / growth & development*
Chemokine CXCL12 / genetics,  metabolism*
Mice
Mice, Transgenic
Phosphorylation
Protein Tyrosine Phosphatase, Non-Receptor Type 11 / genetics,  metabolism*
Receptors, CXCR4 / genetics,  metabolism*
Signal Transduction / physiology
Grant Support
ID/Acronym/Agency:
P30 CA030199/CA/NCI NIH HHS; R01 DK073945/DK/NIDDK NIH HHS; R01 DK073945-02/DK/NIDDK NIH HHS; R01DK73945/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Chemokine CXCL12; 0/Receptors, CXCR4; EC 3.1.3.48/Protein Tyrosine Phosphatase, Non-Receptor Type 11
Comments/Corrections

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