Induction and patterning in Drosophila melanogaster

 

Induction across germ layers is one of the most important mechanisms leading to the complex spatial organization of an animal as it emerges from a fertilized egg. In Drosophila, inductive cell-cell interactions have been described between the ectoderm, the mesoderm and the endoderm. As a result of these processes, positional information is transmitted between adjacent germ layers leading to their correct patterning along the body axis. Numerous signaling pathways have been linked to induction and we have been characterizing one of these in detail, the Dpp/ TGF b pathway.

Our and other groups’ studies led to the identification of a number of gene products that constitute the core Dpp/ TGF b signaling pathway and are involved in signal reception, signal transduction and transcriptional interpretation. In addition to the ligand-activated heteromeric receptor complex and the signal-transducing intracellular Smad proteins, Dpp signaling requires two nuclear proteins, Schnurri (Shn) and Brinker (Brk), to prime cells for Dpp responsiveness. A complex interplay between the nuclear factors involved in Dpp signaling appears to control the transcriptional readout of the Dpp morphogen gradient, and we are trying to characterize this interplay at the molecular level. It remains to be seen whether similar molecular mechanisms operate in the nucleus of vertebrate cells.

During our analysis of a Dpp-responsive enhancer in the developing midgut, we made an interesting and important observation. We found that the Dpp-responsive enhancer of the labial (lab) gene requires for its signal-inducibility a direct interaction with the homeotic selector protein Lab and its cofactors Extradenticle and Homothorax. These results illustrated for the first time how a specific cellular response to Dpp can be generated through synergistic effects on an enhancer carrying both Dpp- and HOX-responsive (signaling- and selector-responsive) sequences. The cooperation of selector and signaling proteins in organ patterning has since received great attention and represents a key mechanism in organ development. We presently try to understand the molecular basis for the synergistic effects of these two classes of molecules.