Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2009-9-15
pubmed:abstractText
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1095-564X
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
334
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
276-84
pubmed:dateRevised
2011-6-16
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Shp2 acts downstream of SDF-1alpha/CXCR4 in guiding granule cell migration during cerebellar development.
pubmed:affiliation
Burnham Institute for Medical Research, La Jolla, CA 92037, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural