Genetic Interaction Screens Identify a Role for Hedgehog Signaling in Drosophila Border Cell Migration

Authors

  • Erika R. Geisbrecht,

    Corresponding author
    • Division of Cell Biology and Biophysics, School of Biological Sciences, University of Missouri-Kansas City, Kansas City, Missouri
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  • Ketki Sawant,

    1. Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio
    2. Department of Biological, Geological, and Environmental Sciences, Cleveland State University, Cleveland, Ohio
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  • Ying Su,

    1. Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio
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  • Ze (Cindy) Liu,

    1. Division of Cell Biology and Biophysics, School of Biological Sciences, University of Missouri-Kansas City, Kansas City, Missouri
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  • Debra L. Silver,

    1. Department of Biological Chemistry, Johns Hopkins School of Medicine, Baltimore, Maryland
    Current affiliation:
    1. Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC
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  • Ashley Burtscher,

    1. Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio
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  • Xuejiao Wang,

    1. Department of Biological Chemistry, Johns Hopkins School of Medicine, Baltimore, Maryland
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  • Alan Jian Zhu,

    1. Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio
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  • Jocelyn A. McDonald

    Corresponding author
    1. Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio
    2. Department of Biological, Geological, and Environmental Sciences, Cleveland State University, Cleveland, Ohio
    • Division of Cell Biology and Biophysics, School of Biological Sciences, University of Missouri-Kansas City, Kansas City, Missouri
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Correspondence to: Erika R. Geisbrecht, Division of Cell Biology and Biophysics, School of Biological Sciences, University of Missouri-Kansas City, Kansas City, MO 64110. E-mail: geisbrechte@umkc.edu and Jocelyn A. McDonald, Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195. E-mail: mcdonaj@ccf.org

Abstract

Background: Cell motility is essential for embryonic development and physiological processes such as the immune response, but also contributes to pathological conditions such as tumor progression and inflammation. However, our understanding of the mechanisms underlying migratory processes is incomplete. Drosophila border cells provide a powerful genetic model to identify the roles of genes that contribute to cell migration. Results: Members of the Hedgehog signaling pathway were uncovered in two independent screens for interactions with the small GTPase Rac and the polarity protein Par-1 in border cell migration. Consistent with a role in migration, multiple Hh signaling components were enriched in the migratory border cells. Interference with Hh signaling by several different methods resulted in incomplete cell migration. Moreover, the polarized distribution of E-Cadherin and a marker of tyrosine kinase activity were altered when Hh signaling was disrupted. Conservation of Hh-Rac and Hh-Par-1 signaling was illustrated in the wing, in which Hh-dependent phenotypes were enhanced by loss of Rac or par-1. Conclusions: We identified a pathway by which Hh signaling connects to Rac and Par-1 in cell migration. These results further highlight the importance of modifier screens in the identification of new genes that function in developmental pathways. Developmental Dynamics 242:414–431, 2013. © 2013 Wiley Periodicals, Inc.

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