Identifying the mechanisms for producing and maintaining neuronal morphology is central to studies of brain development and aging. Several lines of evidence indicate that the pattern of cytoskeletal organization defines neuronal morphology. The experiments of this proposal are aimed at defining mechanisms for elaborating and maintaining cytoskeletal patterns in neurons. The relative plasticity of neuronal shape declines during maturation. This decrease is an important event in neuronal maturation because it ensures that the morphological features produced early in development are maintained during subsequent life. We propose that this decrease in plasticity reflects a corresponding decrease in the plasticity of the cytoskeleton. Microtubules (MT), which are major components of the neuronal cytoskeleton, have labile and stable components; stable MT are not depolymerized by standard MT depolymerizing conditions, while labile MT are. Preliminary studies suggest that the balance between labile and stable MT changes during neuronal maturation. The proposed project will use in vivo and in vitro systems to (1) determine whether the balance between labile and stable MT changes during neuronal development and (2) identify the molecular bases for changes that occur in MT properties during neurite growth. MT are polymers of tubulin and MT-associated proteins (MAPs). Several properties of MAPs suggest that they influence the organization of MT and thereby the cytoskeleton as a whole. The composition of MAPs appears to vary in axons and dendrites of individual neurons. This regional heterogeneity of MAPs has implications for the ability of neurons to generate morphologically distinct domains such as axons and dendrites. The proposed project will use a variety of biochemical and immunological procedures to more fully define the (1) extent of selective partitioning of MAPs in individual neurons and (2) cellular bases for selective partitioning of MT proteins in neurons. The results of these and the above-mentioned studies will relate to the broader issue of how neurons elaborate and maintain the detailed shapes that are so crucial to their functional specialization within the nervous system.
Showing the most recent 10 out of 23 publications
