A calcium-inhibited Drosophila adenylyl cyclase

Mammals possess a family of transmembrane, G-protein-responsive adenylyl cyclase isoforms (tmACs) encoded by distinct genes differing in their patterns of expression and modes of biochemical regulation. Our previous work confirmed that Drosophila melanogaster also possesses a family of tmAC isoforms defining the fly as a suitable genetic model for discerning mammalian tmAC function. We now describe a Drosophila tmAC, DAC39E, which employs a novel means for regulating its expression; differential exon utilization results in a developmental switch in DAC39E protein. DAC39E protein sequence is most closely related to mammalian type III AC, and it is predominantly expressed in the central nervous system (CNS) and olfactory organs, suggesting a role in processing sensory signaling inputs. DAC39E catalytic activity is inhibited by micromolar concentrations of calcium; therefore, DAC39E is oppositely regulated by calcium compared to the only other tmAC shown to be expressed in the Drosophila CNS, Rutabaga AC. The presence of both positively and negatively regulated tmACs suggests a complex mode of cross-talk between cAMP and calcium signal transduction pathways in the fly CNS.     

FGF8-like1 and FGF8-like2 encode putative ligands of the FGF receptor Htl and are required for mesoderm migration in the Drosophila gastrula

BACKGROUND: Mesoderm migration in the Drosophila gastrula depends on the fibroblast growth factor (FGF) receptor Heartless (Htl). During gastrulation Htl is required for adhesive interactions of the mesoderm with the ectoderm and for the generation of protrusive activity of the mesoderm cells during migration. After gastrulation Htl is essential for the differentiation of dorsal mesodermal derivatives. It is not known how Htl is activated, because its ligand has not yet been identified. RESULTS: We performed a genome-wide genetic screen for early zygotic genes and identified seven genomic regions that are required for normal migration of the mesoderm cells during gastrulation. One of these genomic intervals produces upon its deletion a phenocopy of the htl cell migration phenotype. Here we present the genetic and molecular mapping of this genomic region. We identified two genes, FGF8-like1 and FGF8-like2, that encode novel FGF homologs and were only partially annotated in the Drosophila genome. We show that FGF8-like1 and FGF8-like2 are expressed in the neuroectoderm during gastrulation and present evidence that both act in concert to direct cell shape changes during mesodermal cell migration and are required for the activation of the Htl signaling cascade during gastrulation. CONCLUSIONS: We conclude that FGF8-like1 and FGF8-like2 encode two novel Drosophila FGF homologs, which are required for mesodermal cell migration during gastrulation. Our results suggest that FGF8-like1 and FGF8-like2 represent ligands of the Htl FGF receptor.