Research: Mechanisms of spatial and temporal specificity for morphogenesis.
- Mechanisms of development
- HHMI Sea Phages
Morphogenetic processes are necessary for the elaboration of final form in all metazoans. Gastrulation, neural tube formation, and organogenesis all depend on precisely timed, coordinated cell shape changes and whole tissue movements. During many aspects of animal development, endocrine signals provide temporal cues and aid in the proper coordination of these events. However, the mechanisms by which a hormonal signal is transduced to the cellular machinery required for morphogenesis remains largely unknown.
Drosophila provides an ideal model system for defining the hormonal control of morphogenesis. With the large array of molecular and genetic tools currently available and the recent completion of the genome sequence, it is possible to conduct comprehensive screens for genes that function within specific developmental pathways. In addition, endocrine signaling in Drosophila appears to be relatively simple, with a single steroid hormone, 20-hydroxyecdysone, directing all major developmental transitions during the life cycle.
Our current research project exploits the power of Drosophila genetics to gain a comprehensive understanding of how a simple hormonal signal can direct a complex morphogenetic process. We have used sensitized genetic screens to identify new genes that function during morphogenesis of the adult leg. Leg morphogenesis is triggered by the high titer pulse of 20-hydroxyecdysone that also signals the initiation of metamorphosis. Previous studies have demonstrated that the elongation and eversion of the legs are largely driven by cell shape changes dependent on contraction of the actin cytoskeleton. Through cloning and characterizing the mutants that we recovered from these screens, we determined that signaling through the Rho1 small GTPase is necessary to direct the cell shape changes that drive morphogenesis of the adult leg. Rho signaling has been implicated in numerous morphogenetic processes including gastrulation movements during Drosophila embryogenesis, embryonic elongation in C. elegans, and neural tube closure in vertebrates. Our current efforts are aimed at understanding how ecdysone signaling regulates Rho activity in the cell. Furthermore, we are cloning the remaining mutant lines and characterizing their function during Drosophila development using a combination of genetic, molecular-genetic and biochemical approaches.
- Epithelial biology