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- Title
Abi Family Tyrosine Kinases Are Essential for Basement Membrane Integrity and Cortical Lamination in the Cerebellum.
- Authors
Zhaozhu Qiu; Yong Cang; Goff, Stephen P.
- Abstract
The Abi family nonreceptor tyrosine kinases, consisting of closely related Abi and Arg (Abl-related gene), play essential roles in mouse neurulation, but their functions in the subsequent development of CNS are poorly understood. Here, we show that conditional deletion of Abi in precursors of neurons and glia on an Arg knock-out background leads to striking cerebellar malformations, including defects in anterior cerebellar morphogenesis, granule cell ectopia, and hypoplasia. Time course analyses reveal that the abnormal anterior cerebellar foliation results from local disruptions of the basement membrane (BM) located between radial glial endfeet and the meninges during embryonic cerebellar development. Granule cell ectopia and hypoplasia are also associated with the breaches in the BM and abnormal Bergmann glial networks during postnatal cerebellar development. In vitro culture experiments indicate that Abl/Argdeficient granule cells can interact with glial processes and proliferate normally in response to sonic hedgehog compared to cells isolated from control mice. Consistent with these findings, selective ablation of Abl family kinases in cerebellar granule cells alone does not cause any abnormality, suggesting that deletion ofAbl/Argfrom glia is likely required for the mutant phenotype. Together, these results provide compelling evidence that Abl and Arg play key redundant roles in BM maintenance and cortical lamination in the cerebellum.
- Subjects
PROTEIN-tyrosine kinases; CEREBELLUM abnormalities; NEURONS; MORPHOGENESIS; CELL proliferation; LABORATORY mice; BASAL lamina
- Publication
Journal of Neuroscience, 2010, Vol 30, Issue 43, p14430
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.2861-10.2010