Environmental cues play a major role in determining the ultimate fate of the developing nervous system. Our goals are to identify some of the signals recognized by developing neurons as they migrate, differentiate, and form synaptic connections. Previously, as a postdoctoral fellow in the laboratory of Joshua Sanes at Washington University, I identified a component of the synaptic basal lamina of the neuromuscular junction, s-laminin, that is likely to be involved in the stabilization of the mature motor synapse. I obtained antibodies to and cDNA clones for this extracellular matrix molecule, and we are currently developing similar resources for other potentially neuroactive molecules. We plan on using both previously and newly generated antibodies as immunohistochemical and immunopurification tools for identifying the location and function of matrix molecules in the developing nervous system. Similarly, we plan on using previously and newly generated cDNA probes to examine the expression and regulation of these molecules during development. We propose to use immunohistochemical and molecular biological methods to determine where and when s-laminin is expressed in the developing cerebral cortex and olfactory system, and to determine the function of s-laminin in these areas during development, using both in vitro and in vivo systems. In addition, we propose to identify the neural receptor for s-laminin, using purified s-laminin and s-laminin-derived peptides as affinity reagents. Finally, we propose to identify and characterize other matrix components that may be important determinants of development in the central nervous system, using both immunohistochemical and molecular biological techniques. Together, these lines of investigation should help to define the role of extracellular matrix molecules in the development and differentiation of the nervous system.
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