Determination of Neuronal Morphology by Extracellular Matrix
Dennis Higgins Principal Investigator
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Extracellular matrix (ECM) molecules such as laminin and fibronectin stimulate the growth of neuronal processes. The biochemical characterization of these molecules has yielded substantial information about the amino acid sequences which promote neuritic growth and the receptors which mediate this response. However, a fundamental question remains unanswered: what is the nature of the processes which form in the presence of laminin or fibronectin; are they axons or dendrites? To address this issue, Dr. Higgins is currently determining how chronic (1-4 week) exposure to ECM components affects the morphological development of embryonic rat sympathetic neurons in tissue culture. A combination of techniques (intracellular dye injection, immunocytochemistry, electron microscopy) is being used to distinguish axons from dendrites. His preliminary experiments indicate that: 1) laminin promotes only axonal growth in sympathetic neurons; and 2) a basement membrane extract causes the extension of dendrites. These data suggest that axons and dendrites have different growth requirements and that ECM molecules may play a role in determining the shape of sympathetic neurons. This research project will use the same bioassay to determine: 1) are there other neurite-promoting factors which act like laminin in selectively stimulating axonal growth; and 2) what is the identity of the dendrite-program molecule? They will also test the hypothesis that process-specific interactions occur because axons and dendrites have different types of ECM receptors on their surfaces. Such data will help to more clearly define the role of ECM in the morphogenesis of the nervous system.