Cellular and molecular analysis of branching morphogenesis in "Drosophila melanogaster"

In the developing tracheal system of Drosophila melanogaster, six major branches arise by guided cell migration from a sac-like structure. The chemoattractant Branchless/FGF (Bnl) appears to guide cell migration and is essential for the formation of all tracheal branches, while Decapentaplegic (Dpp) signaling is strictly required for the formation of a subset of branches, the dorsal and ventral branches. The aim of this thesis was the analysis of the cellular mechanisms governing tracheal branching morphogenesis and the identification of new genes implicated in this process using large scale gene expression profiling. Using in vivo confocal video microscopy, we find that Bnl/FGF and Dpp signaling affect different cellular functions required for branching morphogenesis. Bnl/FGF signaling affects the formation of dynamic filopodia, possibly controlling cytoskeletal activity and motility as such, while Dpp controls cellular functions allowing branch morphogenesis and outgrowth. Further, we characterized the junctional remodeling events underlying cell intercalation in the dorsal branch and show that unicellularization is not induced by Dpp signaling. Dpp signaling is shown to be mainly required for the repression of sal in the dorsal branch. Therefore concomitant removal of Sal and Kni/Knrl leads to a rescue of dorsal branch formation. We also show that tracheal Sal controls cell-cell adhesion properties, leading to the formation of cell populations with different adhesive properties. These adhesive properties control cell rearrangements and branch formation. Based on these observations, we propose a model for tracheal morphogenesis, whose main features consist of Bnl/FGF induced cytoskeletal activity and motility, and Sal regulated cell adhesion modulation. We also performed an oligonucleotide array screen for Sal and Kni/Knrl targets in the tracheal system. Unfortunately, due to multiple reasons discussed in this thesis, this approach was not successful and had to be abandoned.