title: The Gyc76C Receptor Guanylyl Cyclase and the Foraging cGMP-Dependent Kinase Regulate Extracellular Matrix Organization and BMP Signaling in the Developing Wing of Drosophila melanogaster.
abstract: The developing crossveins of the wing of Drosophila melanogaster are specified by long-range BMP signaling and are especially sensitive to loss of extracellular modulators of BMP signaling such as the Chordin homolog Short gastrulation (Sog). However, the role of the extracellular matrix in BMP signaling and Sog activity in the crossveins has been poorly explored. Using a genetic mosaic screen for mutations that disrupt BMP signaling and posterior crossvein development, we identify Gyc76C, a member of the receptor guanylyl cyclase family that includes mammalian natriuretic peptide receptors. We show that Gyc76C and the soluble cGMP-dependent kinase Foraging, likely linked by cGMP, are necessary for normal refinement and maintenance of long-range BMP signaling in the posterior crossvein. This does not occur through cell-autonomous crosstalk between cGMP and BMP signal transduction, but likely through altered extracellular activity of Sog. We identify a novel pathway leading from Gyc76C to the organization of the wing extracellular matrix by matrix metalloproteinases, and show that both the extracellular matrix and BMP signaling effects are largely mediated by changes in the activity of matrix metalloproteinases. We discuss parallels and differences between this pathway and other examples of cGMP activity in both Drosophila melanogaster and mammalian cells and tissues.
authors.affiliation: Department of Zoology, University of Wisconsin, Madison, Wisconsin, United States of America; Genetics Training Program, University of Wisconsin, Madison, Wisconsin, United States of America.
authors.forename: Justin
authors.initials: J
authors.lastname: Schleede
authors.affiliation: Department of Zoology, University of Wisconsin, Madison, Wisconsin, United States of America.
authors.forename: Seth S
authors.initials: SS
authors.lastname: Blair
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000235:genetics; D006152:Cyclic GMP / Q000235:genetics; D017869:Cyclic GMP-Dependent Protein Kinases / Q000235:genetics* / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism; D006023:Glycoproteins / Q000235:genetics; D006162:Guanylate Cyclase / Q000235:genetics*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics*; D015398:Signal Transduction; D014921:Wings, Animal / Q000254:growth & development* / Q000378:metabolism
chemical_list: D019485:Bone Morphogenetic Proteins; D029721:Drosophila Proteins; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D011956:Receptors, Cell Surface; C091428:sog protein, Drosophila; C054234:chordin; D017869:Cyclic GMP-Dependent Protein Kinases; C528566:for protein, Drosophila; D006162:Guanylate Cyclase; C092949:Gyc76C protein, Drosophila; D006152:Cyclic GMP