The objective of this research is to increase understanding of the role of the cell surface in development and function of hypothalamic magnocellular neurosecretory neurons. Primary aim is to determine if there are plasma membrane molecules which distinguish populations of neurosecretory cells. This question will be addressed by using monoclonal antibodies (MAbs) as probes for antigenic determinants in the plasmalemma. Successful production of such MAbs would make it possible to test several specific hypothesis. Among these are: (1) that specific cell surface molecules mediating strict chemoaffinity mechanisms play a more important role than competitive rearrangement of circuitry during hypothalamic-neurohypophysial development; (2) that glucocorticoids and other hormonal or trophic factors influence cell survival and/or peptide gene expression during neurosecretory differentiation; and (3) that alterations in the concentrations of plasmalemmal molecules mediate the marked plastic changes which occur in the mature magnocellular neurosecretory system. A further technical aim of this research is to apply novel FACS techniques to analysis of neuroendocrine cells. Methods have been developed for purification of rare neuronal populations for use as immunogens for production of cell-type-specific MAbs. The PI's long-term career goal is to broaden the traditional focus of developmental neuroendocrinology by using the magnocellular system to address fundamental questions regarding the mechanisms of differentiation and plasticity in peptidergic neurons.
