Disruption of neuronal migration and radial glia in the developing cerebral cortex following ablation of Cajal-Retzius cells.

Abstract

Cortical neurons are generated within the proliferative layer and follow a strict 'inside-out' gradient of migration and positioning, which determines the characteristic layering and pattern of neural connections in the adult cerebral cortex. Thus, directional migration of postmitotic neuroblasts towards layer I and regulation of the radial glia phenotype subserving cortical migration are central issues in corticogenesis. Recent studies showing that the gene disrupted in the reeler mutation--reelin--is expressed in Cajal-Retzius cells have indicated a role for these pioneer neurons in cortical migration. We show here that ablation of Cajal-Retzius cells in layer I by local application of domoic acid in newborn mice arrests migration of the late-generated neurons, destined to cortical layers II-III, that have been labeled by 5-bromodeoxyuridine injections administered at E16. In addition, degeneration of Cajal-Retzius cells in newborn mice dramatically decreases the number of radial glial apical processes identified by nestin-immunostaining, but increases the number of maturing glial fibrillary acidic protein-positive astrocytes. These findings support an essential role for Cajal-Retzius cells in neuronal migration and corticogenesis, by regulating the identity and function of radial glia and the radial glia-to-astrocyte transformation.