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Proteomics Analysis Identifies Orthologs of Human Chitinase-Like Proteins as Inducers of Tube-Morphogenesis Defects in Drosophila

Sandra G. Zimmerman, Gennifer E. Merrihew, Michael J. MacCoss and Celeste A. Berg
Genetics Early online April 12, 2017; https://doi.org/10.1534/genetics.116.199323
Sandra G. Zimmerman
University of Washington
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Gennifer E. Merrihew
University of Washington
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Michael J. MacCoss
University of Washington
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Celeste A. Berg
University of Washington
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  • For correspondence: caberg@uw.edu
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Abstract

Elevated levels of human chitinase-like proteins (CLPs) are associated with numerous chronic inflammatory diseases and several cancers, often correlating with poor prognosis. Nevertheless, there is scant knowledge of their function. The CLPs normally mediate immune responses and wound healing, and when upregulated, they can promote disease progression by remodeling tissue, activating signaling cascades, stimulating proliferation and migration, and by regulating adhesion. We identified Imaginal disc growth factors (Idgfs), orthologs of human CLPs CHI3L1, CHI3L2, and OVGP1, in a proteomics analysis designed to discover factors that regulate tube morphogenesis in a Drosophila melanogaster model of tube formation. We implemented a novel approach that uses magnetic beads to isolate a small population of specialized ovarian cells, cells that non-autonomously regulate morphogenesis of epithelial tubes that form and secrete eggshell structures called dorsal appendages. Differential mass-spectrometry analysis of these cells detected elevated levels of four of the six Idgf family members (Idgf1, Idgf2, Idgf4, and Idgf6) in flies mutant for Bullwinkle, which encodes a transcription factor and is a known regulator of dorsal-appendage tube morphogenesis. We show that during oogenesis, dysregulation of Idgfs (either gain or loss of function) disrupts the formation of the dorsal-appendage tubes. Previous studies demonstrate roles for Drosophila Idgfs in innate immunity, wound healing, and cell proliferation and motility in cell culture. Here, we identify a novel role for Idgfs in both normal and aberrant tubulogenesis processes.

  • chitinase-like proteins
  • dorsal appendage
  • imaginal disc growth factors
  • morphogenesis
  • proteomics
  • Received December 29, 2016.
  • Accepted April 5, 2017.
  • Copyright © 2017, The Genetics Society of America
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Volume 208 Issue 4, April 2018

Genetics: 208 (4)

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Proteomics Analysis Identifies Orthologs of Human Chitinase-Like Proteins as Inducers of Tube-Morphogenesis Defects in Drosophila

Sandra G. Zimmerman, Gennifer E. Merrihew, Michael J. MacCoss and Celeste A. Berg
Genetics Early online April 12, 2017; https://doi.org/10.1534/genetics.116.199323
Sandra G. Zimmerman
University of Washington
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Gennifer E. Merrihew
University of Washington
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Michael J. MacCoss
University of Washington
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Celeste A. Berg
University of Washington
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  • For correspondence: caberg@uw.edu
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Citation

Proteomics Analysis Identifies Orthologs of Human Chitinase-Like Proteins as Inducers of Tube-Morphogenesis Defects in Drosophila

Sandra G. Zimmerman, Gennifer E. Merrihew, Michael J. MacCoss and Celeste A. Berg
Genetics Early online April 12, 2017; https://doi.org/10.1534/genetics.116.199323
Sandra G. Zimmerman
University of Washington
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gennifer E. Merrihew
University of Washington
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michael J. MacCoss
University of Washington
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Celeste A. Berg
University of Washington
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  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: caberg@uw.edu

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