Jeff Chen


December 2007

Document Type


Degree Name



Dept. of Cell and Developmental Biology


Oregon Health & Science University


Midkine and Pleiotrophin are heparin-binding, secreted small molecules that elicit a variety of process in tissue culture, including neurite outgrowth, branching morphogenesis, chemotaxis, angiogenesis, cell proliferation and survival. Biochemical chemical binding assays have identified a number of molecules that may function as receptors. In this thesis work I investigated the biological functions of Midkine and Pleiotrophin by characterizing the Drosophila homologues Miplel and Miple2. My expression data suggested that miplel is expressed in central nervous system (CNS) glia during embryogenesis, in proliferating cells in the CNS in larvae, and in the mushroom body in the adult brain. miple2 is expressed in the embryonic endoderm and mesoderm, the larval imaginal discs, and the adult gonads. I used a miple2-null mutant to investigate the requirement for Miple2 in Anaplastic lymphoma kinase (Alk) signaling, and in the WinglessIWnt, Hedgehog, Decapentaplegic (Dpp)/TGFP signaling pathways. Combined developmental and genetic data do not support Miple2 as a component in Alk signaling. My results are inconclusive in determining the requirement for Miple2 in Wingless, Hedgehog, and DppITGFP signaling. I also report a potential male sterile phenotype caused by defective sperm individualization in the miple2-null mutants.




School of Medicine



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