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Published on: June 4, 2014
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Cdk5-mediated phosphorylation of RapGEF2 controls neuronal migration in the developing cerebral cortex
Tao Ye1, Jacque P K Ip1, Amy K Y Fu1
11] Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China [2] Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China [3] State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
Nature Communications
|September 6, 2014
Summary
RapGEF2 protein is crucial for pyramidal neuron migration during cerebral cortex development. Its Cdk5-dependent activation regulates neuronal polarity, ensuring proper brain wiring.
Area of Science:
- Neuroscience
- Developmental Biology
- Cell Biology
Background:
- Pyramidal neurons migrate during cerebral cortex development, transitioning from multipolar to bipolar shapes to initiate radial migration.
- Proper neuronal migration and polarity acquisition are essential for correct cortical plate formation and brain wiring.
- The molecular mechanisms initiating and regulating this critical multipolar-bipolar transition remain largely unknown.
Purpose of the Study:
- To investigate the role of Rap1 guanine nucleotide exchange factor 2 (RapGEF2) in regulating neuronal polarity during cerebral cortex development.
- To elucidate the signaling pathway and regulatory mechanisms controlling RapGEF2 activity during neuronal migration.
Main Methods:
- Utilized in utero electroporation in mouse models to introduce genetic constructs into developing cortical neurons.
- Employed live-imaging techniques to observe neuronal migration and polarity dynamics in real-time.
- Investigated the Rap1/N-cadherin signaling pathway and the involvement of Cyclin-dependent kinase 5 (Cdk5) in RapGEF2 regulation.
Main Results:
- RapGEF2 expression is specifically upregulated during the multipolar-bipolar transition phase of neuronal migration.
- RapGEF2 promotes the multipolar-bipolar transition essential for radial migration via the Rap1/N-cadherin pathway.
- Cdk5 phosphorylates and activates RapGEF2, with Cdk5 activity localized to the radial migration zone.
Conclusions:
- RapGEF2 is a key regulator of neuronal polarity during cerebral cortex development.
- Cdk5-mediated phosphorylation of RapGEF2 is essential for initiating the multipolar-bipolar transition in migrating neurons.
- The coordinated action of RapGEF2 and Cdk5 ensures proper neuronal migration and the intricate wiring of the cerebral cortex.
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