Shp2 acts downstream of SDF-1α/CXCR4 in guiding granule cell migration during cerebellar development
| Autor: | Yi Rao, Eric E. Zhang, Guofa Liu, Kazuki Hagihara, Yuehai Ke, Gen-Sheng Feng, Jan-Jan Liu |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Cerebellum
Receptors CXCR4 Cellular differentiation Mice Transgenic Protein Tyrosine Phosphatase Non-Receptor Type 11 Biology Article Glial cell fate specification 03 medical and health sciences Mice 0302 clinical medicine Cell Movement medicine Animals Progenitor cell Phosphorylation Molecular Biology 030304 developmental biology Neuronal cell migration 0303 health sciences Cell growth Brain Cell migration Cell Differentiation Cell Biology Granule cell Brain development Neural stem cell Chemokine CXCL12 Cell biology medicine.anatomical_structure 030217 neurology & neurosurgery Signal Transduction Developmental Biology |
| Zdroj: | Developmental Biology. 334(1):276-284 |
| ISSN: | 0012-1606 |
| DOI: | 10.1016/j.ydbio.2009.07.029 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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