The phenotypic nonspecificity of cell-to-cell signalling in Drosophila melanogaster.

An expectation of a hypothesis that proposes cell-to-cell signalling pathways are redundant due to the redundancy of pathway terminal transcription factors (TFs) was tested by screening 35 signalling ligands (SLs) for rescue of a decapentaplegic (dpp) hypomorphic wing growth phenotype. The screen identified three examples of partial rescue: Hedgehog (HH), Semphorin 1a (SEMA1A) and Wnt ortholog 2 (WNT2). HH overexpression with dppGAL4 may increase the expression of DPP activity from the hypomorphic dpp alleles. However, SEMA1A and WNT2 did not phenocopy ectopic expression of HH or DPP and neither SEMA1A nor WNT2 were required for wing growth suggesting substitution of DPP for partial restoration of wing growth. The WNT2 rescue was dependent on the Frizzled 4 (FZ4) WNT receptor excluding the possibility that WNT2 weakly binds the DPP receptor. Although examples of phenotypic nonspecificity of SL function were identified, this is an expectation, and not direct proof, of the hypothesis of TF redundancy. Screen Report SummaryAn expectation of a hypothesis proposing that cell-to-cell signalling pathways are redundant due to the redundancy of the pathway terminal transcription factors was tested by screening for replacement of one signalling ligand (DPP; SLa) with another SLb for wing growth. Three non-DPP SLs were identified in the screen of 35SLs: HH, SEMA1A and WNT2. Genetic analysis of Sema1a and Wnt2 suggests functional complementation of dpp for wing growth suggesting that SEMA1A and WNT2 partially replace DPP for wing growth. Therefore, an expectation of the hypothesis is met.