The long-term goals of this project are to identify and characterize the trophic requirements of sub-populations of developing spinal motoneurons (MNs) in the chick embryo. The central hypothesis to be tested is that MNs require distinct target-derived trophic agents for their survival depending upon their peripheral targets. For example, cranial MNs or MNs in non-limb innervating regions of the spinal cord may require different trophic factors from MNs that innervate limb muscles; or, within limb-innervating regions, MNs may differ depending on whether they innervate slow vs. fast or flexor vs. extensor muscles. To begin to test this hypothesis the investigator will determine if: (1) MNs express different patterns of trophic factor receptors depending upon their location, synaptic targets or stage of development; (2) neurotrophic factors are differentially expressed in muscle sub-types (fast vs. slow) or in muscles in different regions (e.g. limb vs. non-limb); and (3) Trophic agents administered alone or in combinations selectively promote the survival of MN subtypes and in vivo based on the receptor or ligand expression patterns of MNs identified in aims 1 and 2. The proposed studies are the first systematic attempt to examine the question of whether MNs differ in their trophic requirements during development according to their location, synaptic targets or stage of maturation. In addition to being important for furthering our basic understanding of MN development, the new information generated could potentially be used to devise more rationale of therapeutic strategies for the use of neurotrophic factors in the treatment of MN and other neurodegenerative diseases.
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