Neurogenin 2 controls cortical neuron migration through regulation of Rnd2
Neurogenin 2 controls cortical neuron migration through regulation of Rnd2
Motility is a universal property of newly generated neurons. How cell migration is coordinately regulated with other aspects of neuron production is not well understood. Here we show that the proneural protein neurogenin 2 (Neurog2), which controls neurogenesis in the embryonic cerebral cortex, directly induces the expression of the small GTP-binding protein Rnd2 (ref. 3) in newly generated mouse cortical neurons before they initiate migration. Rnd2 silencing leads to a defect in radial migration of cortical neurons similar to that observed when the Neurog2 gene is deleted. Remarkably, restoring Rnd2 expression in Neurog2-mutant neurons is sufficient to rescue their ability to migrate. Our results identify Rnd2 as a novel essential regulator of neuronal migration in the cerebral cortex and demonstrate that Rnd2 is a major effector of Neurog2 function in the promotion of migration. Thus, a proneural protein controls the complex cellular behaviour of cell migration through a remarkably direct pathway involving the transcriptional activation of a small GTP-binding protein.
- University of Geneva Switzerland
- University of Liège Belgium
- University of Mary United States
- University of Washington United States
- Harborview Medical Center United States
rho GTP-Binding Proteins, Nerve Tissue Proteins, Biochimie, biophysique & biologie moléculaire, Basic Helix-Loop-Helix Transcription Factors/deficiency/genetics/metabolism, Mice, Cell Movement, Basic Helix-Loop-Helix Transcription Factors, Animals, 3' Untranslated Regions, Cell Shape, Cerebral Cortex, Neurons, Enhancer Elements, Genetic/genetics, Nerve Tissue Proteins/deficiency/genetics/metabolism, Gene Expression Regulation, Developmental, Cerebral Cortex/cytology/embryology/metabolism, Life sciences, Enhancer Elements, Genetic, 3' Untranslated Regions/genetics, rho GTP-Binding Proteins/deficiency/genetics/metabolism, Sciences du vivant, RNA Interference, Neurons/cytology/metabolism, Gene Deletion, Biochemistry, biophysics & molecular biology
rho GTP-Binding Proteins, Nerve Tissue Proteins, Biochimie, biophysique & biologie moléculaire, Basic Helix-Loop-Helix Transcription Factors/deficiency/genetics/metabolism, Mice, Cell Movement, Basic Helix-Loop-Helix Transcription Factors, Animals, 3' Untranslated Regions, Cell Shape, Cerebral Cortex, Neurons, Enhancer Elements, Genetic/genetics, Nerve Tissue Proteins/deficiency/genetics/metabolism, Gene Expression Regulation, Developmental, Cerebral Cortex/cytology/embryology/metabolism, Life sciences, Enhancer Elements, Genetic, 3' Untranslated Regions/genetics, rho GTP-Binding Proteins/deficiency/genetics/metabolism, Sciences du vivant, RNA Interference, Neurons/cytology/metabolism, Gene Deletion, Biochemistry, biophysics & molecular biology
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