Absence of Fyn and Src causes a reeler-like phenotype
Absence of Fyn and Src causes a reeler-like phenotype
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DOI：
10.1523/jneurosci.1656-05.2005
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发表时间：
2005-09-14
影响因子：
5.3
通讯作者：
Cooper, JA
中科院分区：
文献类型：
--
作者：
Kuo, G;Arnaud, L;Cooper, JA
Src家族的非受体蛋白酪氨酸激酶调节许多细胞类型的存活、增殖、分化和运动，但它们在脑发育中的作用尚不清楚。生物化学和体外实验表明Src和Fyn参与了Dab1依赖于Reelin的酪氨酸磷酸化，Dab1控制着许多脑区放射状迁移神经元的定位。然而，Src或Fyn介导体内依赖于Reelin的迁移的遗传证据一直缺乏。在这里，我们报告说，虽然Src的是，虽然没有Fyn的中间表型的原因，Src和Fyn的组合缺乏几乎废除Dab1的酪氨酸磷酸化，并导致缺陷的胎儿皮质和小脑非常相似的Dab1突变体的相同年龄。神经发生未受到明显影响，但皮质中神经元的分层被逆转，浦肯野板的形成受损。这意味着Src和Fyn是大脑发育过程中依赖于Reelin的事件所必需的。
Nonreceptor protein tyrosine kinases of the Src family regulate the survival, proliferation, differentiation, and motility of many cell types, but their roles in brain development are unclear. Biochemical and in vitro experiments implicate Src and Fyn in the Reelin-dependent tyrosine phosphorylation of Dab1, which controls the positioning of radially migrating neurons in many brain regions. However, genetic evidence that either Src or Fyn mediates Reelin-dependent migrations in vivo has been lacking. Here, we report that, although Src is dispensable and although the absence of Fyn causes an intermediate phenotype, the combined absence of Src and Fyn almost abolishes tyrosine phosphorylation of Dab1 and causes defects in the fetal cortex and cerebellum very similar to those of dab1 mutants of the same age. Neurogenesis is not detectably affected, but the layering of neurons in the cortex is inverted, and the formation of the Purkinje plate is impaired. This implies that Src and Fyn are needed for Reelin-dependent events during brain development.