Src controls neuronal migration by regulating the activity of FAK and cofilin.

Abstract:

:Migration of postmitotic neurons in the developing cortex along radial glial fiber is essential for the formation of cortical layers. Several neurological diseases are caused by defects in neuronal migration, underlining the importance of this process for brain function. Multiple molecules are involved in this process. However, the precise mechanisms are largely unknown. In the present study, we examined the expression of Src in the developing cortex and investigated the role of Src in neuronal migration and its cellular and molecular mechanisms. Our results showed that Src was strongly expressed in the cerebral cortex during corticogenesis and mainly targeted to the leading processes of migrating neurons. Overexpression of wildtype Src (Src-WT) and its mutants, constitutively active Src (Src-CA) and dominant negative Src (Src-DN) in the mouse brain by in utero electroporation perturbed neuronal migration through affecting the adhesion properties and cytoskeletal dynamics of migrating neurons. Overexpression of Src-WT and Src-CA induced aggregation and branching of migrating neurons, whereas overexpression of Src-DN led to abnormal elongation of the leading processes of migrating neurons. Furthermore, we showed that Src activates the focal adhesion kinase (FAK) and cofilin by regulating their phosphorylation levels. We conclude that Src controls neuronal migration by regulating adhesion properties and F-actin dynamics of migrating neurons.

journal_name

Neuroscience

journal_title

Neuroscience

authors

Wang JT,Song LZ,Li LL,Zhang W,Chai XJ,An L,Chen SL,Frotscher M,Zhao ST

doi

10.1016/j.neuroscience.2015.02.025

subject

Has Abstract

pub_date

2015-04-30 00:00:00

pages

90-100

eissn

0306-4522

issn

1873-7544

pii

S0306-4522(15)00177-3

journal_volume

292

pub_type

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