My research proposal will examine the cellular and molecular properties of tangential migration in the marginal zone of the developing neocortex of the mouse. I will use immunocytochemistry, electron microscopy, and live-imaging techniques in organotypic slice preparation, notably the use of two-photon microscopy in real time. This system, which enables long-term and continuous 3D-imaging for over 48 hours, is an unprecedented opportunity to answer heretofore unattainable questions in the field of neural development. Disruption of tangential migration in the marginal zone may possibly lead to a deficit in GABAergic inhibitory interneurons in the cortex. This deficit may play a role in schizophrenia, epilepsy, and autism. To explore these possibilities I will look at the following specific aims: 1. Characterize the mode, rate, and direction of migration in the marginal zone of the developing neocortex. 2. Determine the immunocytochemical characteristics and place of origin of migrating cells in the marginal zone. 3. Characterize the tangentially migrating cells in the superficial layers of the cortex in Reeler and p35 mutant mice.
