Morphogenetic mechanisms of limb development.
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.
- Zhang, L. and Ward, R.E. Distinct Tissue Distributions and Subcellular Localizations of Differentially Phosphorylated Forms of the Myosin Regulatory Light Chain in Drosophila. In press at Gene Expression Patterns.
- Wang, X. and Ward, R.E. 2010 Sec61a is Required for Dorsal Closure during Drosophila Embryogenesis through its Regulation of Dpp Signaling. Developmental Dynamics 239:784-797.
- Zhang, L. and Ward, R.E. 2009 uniflatable Encodes a Novel Ectodermal Apical Surface Protein Required for Tracheal Inflation inDrosophila. Developmental Biology 336:201-212.
- Patch, K., Stewart, S., Welch, A., and Ward, R.E. 2009. A Second-site Noncomplementation Screen for Modifiers of Rho1 Signaling during Imaginal Disc Morphogenesis. PLoS ONE 4:e7574.
- Chen, X., Mei, L., and Ward, R. 2008. Protein Function Assignment through Mining Cross-Species Protein-Protein Interactions. PLoS ONE 3:e1562.
- Ward, R.E., Evans, J.J., and Thummel, C.S. 2003. Genetic Modifier Screens in Drosophila Demonstrate a Role for Rho1 Signaling in Ecdysone-Triggered Imaginal Disc Morphogenesis. Genetics 165:1397–1415.
- *Ward, R.E., *Reid, P., *Bashirullah, A., Dfavino, P.P., and Thummel, C.S. 2003. GFP in Living Animals Reveals Dynamic Developmental Responses to Ecdysone during Drosophila Metamorphosis. DevelopmentalBiology 256:389–402. (*co-principle authors)
- Tepass, U., Tanentzapf G., Ward, R.E., and Fehon, R.G. 2001. Epithelial Cell Polarity and Cell Junctions in Drosophila. Annual Review of Genetics 35:747–784.
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