Axogial communication mediated by soluble neuregulin-1 and bdnf

AXOGIAL COMMUNICATION MEDIATED BY SOLUBLE NEUREGULIN-1 AND BDNFbyZHENZHONG MAAugust 2011Advisor: Jeffrey A. Loeb, M.D., Ph.D.Major: Molecular Biology & GeneticsDegree: Doctor of PhilosophyDuring peripheral nervous system development, successful communication betweenaxons and glial cells including Schwann cells in peripheral nervous system andoligodendrocytes in central nervous system, is required for the proper functions of bothneurons and glia. Three types of alternatively-spliced proteins belonging to theneuregulin1 (NRG1) gene family of growth and differentiation factors are essential forSchwann cell survival and peripheral nerve development. While membrane-boundNRG1 forms (type III) has been strongly implicated in the regulation of myelinationprocess at late stage of Schwann cell development, little is known about the role ofsoluble, heparin-binding forms of NRG1 (type I/II) in regulating early Schwann celldevelopment in vivo. These forms are rapidly released from axons in vitro by Schwanncell-secreted neurotrophic factors, and, unlike membrane-bound forms, have a uniqueability to diffuse and adhere to heparan sulfate-rich cell surfaces. We harness this naturaltargeting ability of soluble NRG1 to develop a novel antagonist by fusing itsheparin-binding domain (HBD) to the soluble human epidermal growth factor receptor 4