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.

Receptor-Type Guanylyl Cyclase at 76C (Gyc76C) Regulates De Novo Lumen Formation during Drosophila Tracheal Development

“…We also showed that Gyc76C is required during muscle development for proper localization of integrins at sites of contact between the body wall muscles and tendon cells [ 19 ]. Consistent with our demonstration of a role for gyc76C and for in integrin-dependent adhesion, recent studies in the developing wing show that gyc76C and for regulate ECM-remodeling matrix metalloproteinases [ 20 ]. Although we reported gyc76C to be expressed in the developing trachea [ 19 ], it was previously not known what role gyc76C played in tracheal development.…”

Distinct functions of a cGMP-dependent protein kinase in nerve terminal growth and synaptic vesicle cycling

“…This suggests that FOR acts through Mav and Gbb to negatively regulate nerve terminal growth, although it remains possible that FOR functions in a parallel pathway to Mav and Gbb. Interestingly, FOR also regulates TGF-β/BMP signalling in the developing wing of Drosophila (Schleede and Blair, 2015). PKG regulates intracellular Ca 2+ levels in rat glial cell cultures (Willmott et al, 2000).…”

Effect of Guanylate Cyclase-22-like on Ovarian Development of Orius nagaii (Hemiptera: Anthocoridae)

“…RNAi of Vg in insects such as Nilaparvata lugens [41], Bemisia tabaci [42], and Panonychus citri [43] can inhibit ovarian development and reduce egg production, while RNAi-mediated suppression of Vg expression in adult Cimex lectularius females drastically reduced egg production, and resulted in atrophied ovaries and an inflated abdomen caused by hypertrophied fat bodies [44]. In Drosophila, GCY is associated with memory and embryonic cell development [45][46][47]. In C. elegans, GCY is also involved in body development, but more reports have focused on neural mechanisms [20,21].…”