Cdk5 phosphorylation of ErbB4 is crucial for cortical interneuron migration
View/ Open
ICR Author
Author
Rakic, S
Kanatani, S
Hunt, D
Faux, C
Cariboni, C
Chiara, F
Khan, S
Wansbury, O
Howard, BA
Nakajima, K
Nikolic, M
Parnavelas, JG
Type
Journal Article
Metadata
Show full item recordAbstract
Interneuron dysfunction is often associated with neurological and psychiatric disorders, such
as epilepsy, schizophrenia and autism. Some of these disorders arise during brain formation, at the
time of interneuron specification, migration and synapse formation. Here, we showed that the
signalling molecule cyclin-dependent kinase 5 (Cdk5), and its activator p35, control the migration of
interneurons towards and within the cerebral cortex by modulating the motogenic
ErbB4/phosphatidylinositol (PI) 3-kinase signalling pathway. We first identified ErbB4 as a novel
p35/Cdk5 kinase substrate. We then demonstrated that Cdk5-dependent ErbB4/PI3-kinase signalling
cascade regulates interneuron leading process dynamics (morphology) and directionality. Finally, we
showed that lack of Cdk5 activity in p35 mutants leads to permanent reduction in the final number of a
subtype of interneurons that may affect formation of neuronal circuits, thus increasing the risk of
neurodevelopmental disorders. Together, these findings identify Cdk5 as a crucial signalling factor in
cortical interneuron development.
Collections
Research team
Endocrine control mechanisms
Language
eng
Date accepted
2013-08-01
License start date
2013-08-01
Citation
under review at Development