| Shp2 acts downstream of SDF-1alpha/CXCR4 in guiding granule cell migration during cerebellar development. | |
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MedLine Citation:
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PMID: 19635473 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Kazuki Hagihara; Eric E Zhang; Yue-Hai Ke; Guofa Liu; Jan-Jan Liu; Yi Rao; Gen-Sheng Feng |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2009-07-25 |
Journal Detail:
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Title: Developmental biology Volume: 334 ISSN: 1095-564X ISO Abbreviation: Dev. Biol. Publication Date: 2009 Oct |
Date Detail:
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Created Date: 2009-09-15 Completed Date: 2009-12-29 Revised Date: 2011-06-16 |
Medline Journal Info:
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Nlm Unique ID: 0372762 Medline TA: Dev Biol Country: United States |
Other Details:
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Languages: eng Pagination: 276-84 Citation Subset: IM |
Affiliation:
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Burnham Institute for Medical Research, La Jolla, CA 92037, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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R01 DK073945-02/DK/NIDDK NIH HHS; R01DK73945/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Chemokine CXCL12; 0/Receptors, CXCR4; EC 3.1.3.48/Protein Tyrosine Phosphatase, Non-Receptor Type 11 |
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