What are the signals for neuronal migration that determine how neurons reach their appropriate positions in the developing cerebral cortex?
Different classes of neurons of the cerebral cortex arrive at their laminar and areal locations using distinct patterns of migration. Pyramidal cortical neurons migrate radially from their birth places in the dorsal telencephalic ventricular zone, primarily by using the radial glial scaffold or the inherited leading process of a radial glial parent cell, as a template for their oriented migration. Interneurons, arising from the ganglionic eminence, migrate tangentially into the developing cerebral wall along the marginal zone as well as through the intermediate zone in a presumed radial glial independent manner, using corticofugal fibers as substrates. A subset of these interneurons navigate radially inwards toward the ventricular zone before turning back to migrate towards the cortical plate. How interneurons migrate and position themselves in the appropriate laminar and areal locations can influence the patterns of their connectivity and function. The altered function of GABAergic interneurons in the forebrain is thought to contribute to the cognitive functional deficits in neurodevelopmental disorders such as schizophrenia. Neuregulin1 (NRG1)-ErbB4 interactions are essential for the generation and guidance of interneurons in the embryonic and adult forebrain and disrupted NRG1-ErbB4 signaling is evident in schizophrenic brains. An understanding of the NRG1-ErbB4 regulated mechanisms that modulate the navigation and functional differentiation of interneurons in the forebrain can help delineate the pathophysiological processes that culminate in schizophrenia. Thus we are using NRG1-ErbB4 signaling as a molecular model and long- term live imaging of interneurons as a tool to examine the mechanisms that influence the generation, movement and placement of interneurons within appropriate areal and laminar locations in the developing cerebral cortex.