A molecular link between FGF and Dpp signaling in branch-specific migration of the Drosophila trachea

The tracheal system of Drosophila embryos achieves its archetypal branching pattern through a series of cell migration events requiring the FGF, Dpp, and Wg/WNT signaling pathways. To gain insight into tracheal cell migration, we performed an F4 EMS mutagenesis screen to generate and characterize new mutations resulting in tracheal defects. From 2591 mutagenized third chromosome lines, we identified 33 mutations with defects in tracheal development, corresponding to 12 distinct complementation groups. The new mutations included novel hypomorphic alleles of the FGF receptor gene, breathless, and the ETS-domain transcription factor gene, pointed. We show that reduced function of either breathless or pointed specifically affects migration of the dorsal and ventral tracheal branches, more specific functions than previously described for these genes. Our analysis reveals that breathless and pointed control dorsal branch migration through transcriptional regulation of the Dpp pathway effectors, Knirps and Knirps-related, which are necessary for migration of this branch. We further show that expression of knirps or knirps-related rescues dorsal but not ventral branch migration in the breathless hypomorph. These studies support a model in which both the Dpp- and the FGF-signaling pathways control expression of knirps and knirps-related, thereby regulating cell migration during dorsal branch formation.