Proper midgut patterning requires cooperation between two BMP signaling molecules, Gbb and Dpp, and regulation of the BMP signal by a homeotic gene. C. Savery , K. Wharton. Molec Biol/Cell Biol & Biochem, Brown Univ, Providence, RI.

   Bone Morphogenetic Proteins (BMPs) are a family of extracellular signaling molecules that are essential in vertebrates and invertebrates for many processes including cell fate specification, proliferation and tissue maintenance. A common theme emerging from studies on BMPs is that they are often expressed in overlapping domains and more than one BMP is required for a particular process. The embryonic midgut of Drosophila is one example of an organ that requires two BMPs, encoded by the glass bottom boat (gbb) and decapentaplegic (dpp) genes, for its proper development. The hallmarks of a properly patterned gut include the formation of three morphological constrictions and elongation of the gastric caecae (four blind ended tubes) from the anterior of the midgut. gbb and dpp mutants both exhibit defects in midgut patterning where gbb mutants lack gastric caecae and the most anterior constriction while dpp mutants lack gastric caecae and the central constriction. The role of dpp in midgut patterning has been well characterized but we would like to understand how gbb contributes to this process as well as determine how the two BMPs coordinate to pattern a tissue. By utilizing an antibody to phosphorylated Mad (pMad, the activated form of a downstream component), we have mapped regions of BMP signaling during midgut development. We have found that Gbb and Dpp signaling is often temporally and spatially distinct but there are also regions where neither BMP can signal without the presence of the other suggesting that heterodimers may be required. Furthermore, we will present evidence that BMP signaling is regulated by the homeotic gene Antennapedia (Antp). We have found that Antp represses expression of a gbb target and production of pMad in parasegment 4 just anterior to where Antp is expressed in the visceral mesoderm. We are currently testing several other candidate genes that may genetically interact with gbb. We will present data from these studies as well.