CHEMOKINE SYNERGY WITH PDGF--OLIGODENDROCYTE PRECURSORS

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DESCRIPTION: The purpose of this project is to characterize the role of GRO-a, an a-chemokine recently demonstrated by Dr. Miller's laboratory to be a major environmental factor that modulates the response of oligodendrocyte precursors to PDGF. In the first Specific Aim, the chemokine structural motifs required to enhance the PDGF proliferation response of oligodendrocyte precursors will be defined. In the second Specific Aim, the applicant intends to establish optimal conditions for interactions between GRO-alpha and PDGF to elicit oligodendrocyte precursor chemotaxis, and the capacity of GRO-alpha to enhance PDGF receptor signaling. In the third Specific Aim, molecular mechanisms of GRO-alpha action will be elucidated by evaluating ligand binding characteristics, as well as by determining the involvement of calcium and G proteins in signal transduction cascade. In the fourth Specific Aim, the distribution of biologically effective chemokines in the developing spinal cord will be determined.