Molecular and cellular mechanisms of DCX family proteins in brain development

Doublecortin（Dcx）和Doublecortin样激酶（Dclk 1、Dclk 2）在皮质层形成以及轴突和树突形成中协同起作用，这是正确的神经回路形成所需的。DCX家族蛋白的缺失与癫痫的发生密切相关，本研究发现了DCLK 1的一个新靶点MAP 7 D1。皮层2/3层锥体细胞中MAP 7 D1的耗尽导致胼胝体中轴突伸长受损。过表达的非磷酸化突变体MAP 7 D1，而不是野生型MAP 7 D1，也损害胼胝体轴突伸长。这些结果表明，通过DCLK 1磷酸化的MAP 7 D1调节神经元中轴突的伸长。

Doublecortin (Dcx) and Doublecortin-like kinases (Dclk1, Dclk2) function cooperatively in cortical layer formation and axon and dendrite formation that is required for the proper neural circuit formation. DCX family proteins deficiency is associated with epilepsy.In this project, we identified a novel target of DCLK1, MAP7D1. Depletion of MAP7D1 in cortical layer 2/3 pyramidal cells resulted in impaired axon elongation in the corpus callosum. Overexpression of unphosphorylated mutant MAP7D1, but not wild-type MAP7D1, also impaired callosal axon elongation. These results suggested that phosphorylation of MAP7D1 by DCLK1 regulate axon elongation in neurons.