Cellular and Molecular Mechanisms Controlling Pyramidal Neuron and Interneuron Migration in the Developing Neocortex

The development of the mammalian neocortex is contingent upon the successful migration of excitatory pyramidal neurons and inhibitory interneurons to the cortical plate. Pyramidal neurons migrate from the ventricular zones of the dorsal telencephalon along a radial glial scaffold, while interneurons migrate tangentially from the ventral telencephalon with no required substrate. The aim of my dissertation was to find the mechanisms by which these two distinct neuronal populations achieve the same task of migrating to the appropriate cortical position in spite of their differences. In pyramidal neurons, I characterized the role of Neurogenin2 (Ngn2) in specifying the migration properties and the dendritic morphology of pyramidal neurons by implementing confocal time-lapse microscopy and developing quantitative image analysis tools. In interneurons, I identified a novel molecular mechanism underlying the termination of their migration. I demonstrated that of GABAA receptor activation by ambient GABA is necessary and sufficient to stop interneurons migration an effect requiring theupregulation of the potassium chloride co-transporter, KCC2. Taken together, my work has improved our understanding of some of the molecular mechanisms controlling the proper migration of pyramidal and non-pyramidal neurons during cortical development.