Abstract
During cortical development, newly generated neurons migrate radially toward their final positions. Although several candidate genes essential for this radial migration have been reported, the signaling pathways regulating it are largely unclear. Here we studied the role of phosphatidylinositol (PI) 3-kinase and its downstream signaling molecules in the radial migration of cortical neurons in vivo and in vitro. The expression of constitutively active and dominant-negative PI 3-kinases markedly inhibited radial migration. In the neocortical slice culture, a PI 3-kinase inhibitor suppressed the formation of GTP-bound Rac1 and Cdc42 and radial migration. Constitutively active and dominant-negative forms of Rac1 and Cdc42 but not Akt also significantly inhibited radial migration. In migrating neurons, wild-type Rac1 and Cdc42 showed different localizations; Rac1 localized to the plasma membrane and Cdc42 to the perinuclear region on the side of the leading processes. These results suggest that both the PI 3-kinase/Rac1 and Cdc42 pathways are involved in the radial migration of cortical neurons and that they have different roles.
Highlights
During mammalian cortical development, neurons born in the cortical ventricular zone migrate radially, resulting in the inside-out formation of the cortical plate, which is composed of six layers
Wild-type Rac1 and Cdc42 showed different localizations; Rac1 localized to the plasma membrane and Cdc42 to the perinuclear region on the side of the leading processes. These results suggest that both the PI 3-kinase/Rac1 and Cdc42 pathways are involved in the radial migration of cortical neurons and that they have different roles
To investigate the role of PI 3-kinase and its downstream signaling molecules in the radial migration of cortical neurons, we performed in utero electroporation to introduce expression vectors encoding GFP with or without signaling molecules into neuronal progenitor cells at the cortical VZ of embryonic brains at E15.5, and we analyzed the radial migration of the labeled neurons in the cerebral cortex
Summary
Neurons born in the cortical ventricular zone migrate radially, resulting in the inside-out formation of the cortical plate, which is composed of six layers. These results suggest that both the PI 3-kinase/Rac1 and Cdc42 pathways are involved in the radial migration of cortical neurons and that they have different roles. These results suggest different roles for the PI 3-kinase/Rac1 and Cdc42 pathways in the radial migration of cortical neurons.
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