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C3G regulates cortical neuron migration, preplate splitting and radial glial cell attachment
- Source :
- Development (Cambridge, England). 135(12)
- Publication Year :
- 2008
-
Abstract
- Neuronal migration is integral to the development of the cerebral cortex and higher brain function. Cortical neuron migration defects lead to mental disorders such as lissencephaly and epilepsy. Interaction of neurons with their extracellular environment regulates cortical neuron migration through cell surface receptors. However, it is unclear how the signals from extracellular matrix proteins are transduced intracellularly. We report here that mouse embryos lacking the Ras family guanine nucleotide exchange factor,C3G (Rapgef1, Grf2), exhibit a cortical neuron migration defect resulting in a failure to split the preplate into marginal zone and subplate and a failure to form a cortical plate. C3G-deficient cortical neurons fail to migrate. Instead, they arrest in a multipolar state and accumulate below the preplate. The basement membrane is disrupted and radial glial processes are disorganised and lack attachment in C3G-deficient brains. C3G is activated in response to reelin in cortical neurons, which, in turn, leads to activation of the small GTPase Rap1. In C3G-deficient cells, Rap1 GTP loading in response to reelin stimulation is reduced. In conclusion, the Ras family regulator C3G is essential for two aspects of cortex development, namely radial glial attachment and neuronal migration.
- Subjects :
- Lissencephaly
Mice, Inbred Strains
Mice
Organ Culture Techniques
Cell Movement
Subplate
medicine
Cell Adhesion
Animals
Reelin
Molecular Biology
Cells, Cultured
Crosses, Genetic
Guanine Nucleotide-Releasing Factor 2
Cerebral Cortex
Neurons
biology
Stem Cells
Anatomy
medicine.disease
Embryo, Mammalian
Radial glial cell
Cell biology
Corticogenesis
Reelin Protein
medicine.anatomical_structure
nervous system
Cerebral cortex
Mutation
biology.protein
Mice, Inbred CBA
Neuroglia
Rap1
Developmental Biology
Subjects
Details
- ISSN :
- 09501991
- Volume :
- 135
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- Development (Cambridge, England)
- Accession number :
- edsair.doi.dedup.....44461f9114851d5a1206425a569e5d47