Patterning and morphogenesis of the Drosophila leg

During development groups of cells undergo coordinated rearrangements to generate complex morphological structures. Patterning signals and transcription factors first determine the identity of future structures and then cellular remodeling processes mediate the morphogenesis of the tissue to generate the final form. The leg imaginal disc serves as a useful genetic model to study the control of patterning and tissue morphogenesis. Although many of the signaling molecules and transcription factors that generate the major subdivisions of the leg have been identified, the genes involved in the fine patterning of the leg, as well as the genes that subsequently reshape the topology of the epithelium, remain to be elucidated. In the first part of this work, we examined the contribution of the genes lines and bowl to the organization of the proximo-distal (PD) axis and the subdivision of the leg PD axis into a series of segments. We find that the genes lines and bowl play an important role during early larval stages in patterning the Drosophila tarsus along the proximo-distal axis. Later during segmentation, lines and bowl contribute to generating a stable Notch signaling interface between Dl-expressing cells and adjacent distal cell in the distal region of each leg segment. This interface is important for leg segment growth and joint morphogenesis.;In the second part, we examined the role of the RhoGTPase regulators, the Rho GTPase activating proteins (RhoGAPs) and Rho guanine nucleotide exchange factors (RhoGEFs) during tarsal joint morphogenesis. Members of the Rho family of GTPases have been implicated in regulating various morphogenetic processes. By examining the transcriptional expression of RhoGTPase regulators involved in leg morphogenesis we identify restricted expression patterns for 12 out of the 20 RhoGEFs and 10 out of the 22 RhoGAPs encoded in Drosophila during metamorphosis. By conducting a targeted RNA interference (RNAi) screen we identify several joint-specific RhoGAPs and RhoGEFs, which act downstream of segmental patterning signals to control epithelial morphogenesis. We characterize the role of RhoGAP68F and provide evidence that it localizes with Rab4 recycling endosomes and acts to attenuate their recycling. We propose that by inhibiting endocytic recycling RhoGAP68F facilitates apical constriction of joint morphogenesis.