branchless Encodes a Drosophila FGF Homolog That Controls Tracheal Cell Migration and the Pattern of Branching

TLDR

The molecular basis for patterning complex organ structures such as the lung and insect tracheal system is unknown. We describe the Drosophila gene branchless (bnl) and show it is a key determinant of tracheal branching pattern. bnl encodes an FGF homolog that functions as a ligand for the breathless receptor tyrosine kinase expressed on developing tracheal cells. bnl is essential for tracheal branching, expressed in clusters at future branch sites, and its misexpression can redirect or expand branching, indicating that the FGF pathway guides tracheal cell migration and activates subsequent branching programs.

Abstract

The molecular basis for patterning of complex organ structures like the lung and insect tracheal system is unknown. Here, we describe the Drosophila gene branchless (bnl ) and demonstrate that it is a key determinant of the tracheal branching pattern. bnl is required for tracheal branching and is expressed dynamically in clusters of cells surrounding the developing tracheal system at each position where a new branch will form and grow out. Localized misexpression of bnl can direct branch formation and outgrowth to new positions. Generalized misexpression activates later programs of tracheal gene expression and branching, resulting in massive networks of branches. bnl encodes a homolog of mammalian fibroblast growth factors (FGFs) and appears to function as a ligand for the breathless receptor tyrosine kinase, an FGF receptor homolog expressed on developing tracheal cells. The results suggest that this FGF pathway specifies the tracheal branching pattern by guiding tracheal cell migration during primary branch formation and then activating later programs of finer branching at the ends of growing primary branches.