STOP SIGNALS FOR NEURONAL MIGRATION IN CEREBRAL CORTEX

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Description (Verbatim from the applicant's abstract): Neuronal migration on radial glia and other neural substrates enables the deployment of accurate numbers of neurons at the right time into appropriate locations, where they interact with various inputs to produce the characteristic synaptic connectivity and laminar organization of the mammalian cerebral cortex. Abnormalities in neuronal migration on radial glia, and radial glial development lead to aberrant placement and connectivity of neurons in human brain, an underlying cause of brain disorders such as schizophrenia. Thus, elucidation of mechanisms that determine how neurons reach their appropriate positions in the developing cerebral cortex would help in understanding normal cortical development as well as in deciphering the pathogenesis of various developmental brain disorders. To study radial glial cell surface molecules that function to signal cortical neurons to stop at the appropriate laminar location in the developing cerebral cortex, we identified a putatively novel radial glial cell surface molecule (Radial Glial Stop Signal molecule: RAGS 1) whose temporal and spatial distribution during cortical development in regions where neurons terminate their migration suggest that it may function as a positional indicator to migrating neurons, signaling them that they have arrived at the appropriate location in the developing cortical plate. Here, we propose to elucidate (1) its functional importance, primarily by studying the outcome of interference with the biological activity of this molecule during cortical development, and (2) decipher its molecular characteristics. In combination, the functional and molecular characterization of this radial glial antigen will help in understanding the role neuron-glial interactions play in the emergence of laminar organization of the cerebral cortex as well as in deciphering the pathogenesis of various developmental brain disorders affecting mental health.