Regulation of epithelial morphogenesis by overlapping expression of Folded gastrulation (Fog), and its receptor, Mist. Alyssa J. Manning, Kimberly Peters, Stephen L. Rogers. Biology Department, UNC-Chapel Hill, Chapel Hill, NC.

   Understanding morphogenesis, the set of processes by which cells are rearranged and change shape to form organs and other higher-order structures, is crucial to our knowledge of biology. The Folded gastrulation (Fog)-Concertina (Cta) signaling pathway necessary for Drosophila epithelial folding is a fantastic system to study the principles morphogenesis. During gastrulation, a signal from the secreted protein Fog is received by cells of the presumptive mesoderm. Then, the G protein, Cta, is activated, which causes a signaling cascade to induce actin-based apical constriction and invagination of these cells. This same signaling pathway also controls other morphogenetic events, including invagination of the posterior midgut during embryogenesis and folding of imaginal discs during larval development. We have used RNAi screening in cell culture to discover a GPCR, Mist, which is a Fog receptor. mist RNA is specifically expressed in folds of imaginal discs, the presumptive mesoderm, and the posterior midgut. Specification and invagination of the mesoderm are induced by two transcription factors, Twist and Snail, which are specifically expressed in the mesoderm. Precisely patterned transcription of fog in this tissue is known to be activated by Twist. We now show that Snail is necessary for mist expression in the mesoderm. To test whether Mist is involved in morphogenesis in imaginal discs we altered levels of Mist, Fog, or Cta by RNAi and overexpression. Each of these molecules normal expression levels and patterning is necessary for proper folding patterns. We have also made a deletion allele which disrupts mist expression by imprecise P-element excision. This allele shows that mist expression is also required for proper gastrulation movements. mist mutants phenocopy Fog and Cta mutants, exhibiting twisted gastrulation and improper invagination of mesodermal cells. Our data reveals that Fog and its receptor, Mist, are both patterned to robustly control the location and timing of epithelial morphogenesis in Drosophila.