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Cdk5 phosphorylation of ErbB4 is required for tangential migration of cortical interneurons.

ABSTRACT: Interneuron dysfunction in humans is often associated with neurological and psychiatric disorders, such as epilepsy, schizophrenia, and autism. Some of these disorders are believed to emerge during brain formation, at the time of interneuron specification, migration, and synapse formation. Here, using a mouse model and a host of histological and molecular biological techniques, we report that the signaling molecule cyclin-dependent kinase 5 (Cdk5), and its activator p35, control the tangential migration of interneurons toward and within the cerebral cortex by modulating the critical neurodevelopmental signaling pathway, ErbB4/phosphatidylinositol 3-kinase, that has been repeatedly linked to schizophrenia. This finding identifies Cdk5 as a crucial signaling factor in cortical interneuron development in mammals.

SUBMITTER: Rakic S

PROVIDER: S-EPMC4380000 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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Cdk5 phosphorylation of ErbB4 is required for tangential migration of cortical interneurons.

Rakić Sonja S Kanatani Shigeaki S Hunt David D Faux Clare C Cariboni Anna A Chiara Francesca F Khan Shabana S Wansbury Olivia O Howard Beatrice B Nakajima Kazunori K Nikolić Margareta M Parnavelas John G JG

Cerebral cortex (New York, N.Y. : 1991) 20131018 4

Interneuron dysfunction in humans is often associated with neurological and psychiatric disorders, such as epilepsy, schizophrenia, and autism. Some of these disorders are believed to emerge during brain formation, at the time of interneuron specification, migration, and synapse formation. Here, using a mouse model and a host of histological and molecular biological techniques, we report that the signaling molecule cyclin-dependent kinase 5 (Cdk5), and its activator p35, control the tangential m ...[more]

PMID: 24142862

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