Fog mediated G-protein coupled receptor signaling

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Folded gastrulation (Fog) is a secreted ligand that signals through the G-protein-coupled receptors Mist and Smog and the G-protein Concertina to activate downstream effectors to elicit cell-shape change during gastrulation. In the embryonic central nervous system (CNS), Fog has roles in axon guidance and glial morphogenesis. However, the elements of the pathway as well as mechanisms required for transducing the signal in this context have not been determined.

Cells undergo change in shape during development to facilitate processes like cell migration, tissue extension, and tube formation, which are essential for organ formation. In Drosophila, G-coupled protein receptor (GPCR) signaling triggered by the ligand Folded gastrulation (Fog) brings about co-ordinated apical constriction essential for cell invagination during gastrulation.

Fog signaling is conserved in the CNS, and its regulation in this context, is still poorly understood. In an earlier study, the orphan receptor tyrosine phosphatase PTP52F was shown to function as a positive regulator of Fog signaling. Consistent with this role, ptp52F mutant embryos showed presence of an irregular ventral furrow similar to fog mutants. The overlap in expression and function of Fog and Htl signaling in LG and their common role in regulating morphogenesis, prompted us to test whether Htl might regulate Fog signaling in the CNS. In the embryonic CNS, expression of fog is enriched in a subset of LG and downregulation of the gene leads to LG becoming smaller and more spherical in shape. We knocked down concertina in glia using RNAi and found that it exerts a similar effect: the LG were smaller in size and more spherical. This phenotype asthe strong similarity between glia and neurons in their response to Fog overexpression, implying that results from one can be extended to the other. This, coupled with the ease with which one can score AMC, prompted us to choose this as an assay to evaluate all subsequent genetic interactions. In terms of morphology, the glia appeared stretched and more tightly packed. Interestingly, overexpression of concertina did not significantly alter glial organization; however, expression of a constitutively active Concertina (UAS-ctaQ303L/UAS-ctaCA) led to severe defects and embryonic lethality: LG appeared scattered and stretched. In addition, the CNS in these embryos failed to condense.

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