Over the course of embryonic development, undifferentiated neuroepithelial cells proliferate and give rise to the enormous variety of neurons that populate the CNS. During their development, young cerebral cortical neuron must make many choices about where to migrate, what layer to sit in, and wh t kind of axonal connections to form. The goal of this research is to begin to identify the cellular and molecular processes by which young neurons in the developing visual cortex achieve their normal fates. Five specific issues are under study: (1) Visual cortical neurons that are normally destined to sit in layers 5 and 6 will be challenged to alter thei normal fates by heterochronic transplantion into the brains of neonatal hos ferrets. These experiments address the question of whether the actual site of a neuron's final mitotic division determines its laminar position. (2) The cellular processes that sculpt a neuron's dendritic morphology and loca axonal connections will be explored by pitting intrinsic and extrinsic cues against one another in heterochronic transplants. Intracellular injections of Lucifer Yellow will then be made into the transplanted neurons in tissue slices through area 17. (3) Neurons normally destined for layer 2/3 will b transplanted into the brains of fetal hosts (in which deep-layer neurons ar being generated) in order to ask whether presumptive upper-layer neurons ar committed to their normal identities. (4) To test whether CNS neurons use common molecular mechanisms for migration along radial glia, cerebellar granule cells will be transplanted into the occipital cerebral mantle and their migratory abilities in this foreign environment will be assayed. (5) The molecular mechanisms of laminar specificity will be explored with an in vitro assay for laminar recognition by developing visual cortical neurons. These results should contribute to our understanding of the cellular and molecular basis of neuronal migration and the formation of specific connections in the visual system. They may furthermore suggest new strategies for the treatment of developmental brain disorders in humans, in which neuronal migration or specific synapse formation has gone awry.
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