Animal development is critically dependent upon precisely timed and orchestrated morphogenetic processes including cell shape changes and rearrangements. These morphogenetic events are triggered and controlled by developmentally regulated signaling pathways that lead to cytoskeletal dynamics in individual cells. These forces must then be propagated through the epithelium and maintained in order to elicit appropriate tissue-level morphological changes. These latter steps are dependent on emergent properties of the tissue including the viscosity and elasticity of the epithelium, the stiffness of the membranes and the mechanical properties of the extracellular matrix. An effective way to define novel mechanisms that contribute to these emergent properties is through the characterization of mutations recovered in genetic screens of morphogenesis. Through a series of genetic screens in the fruit fly, Drosophila melanogaster, we have identified a complex of interacting proteins that localize to the lateral membrane as playing critical roles in morphogenetic processes throughout fly development. These proteins ultimately form the septate junction, the primary occluding junction in invertebrate epithelia, however, their role in morphogenesis appears to be independent of this occluding function. Our current projects aim to gain a mechanistic understanding of how these proteins affect adhesion, cytoskeletal dynamics and tissue polarity during morphogenesis at various stages of development including oogenesis, embryogenesis, and metamorphosis.
In a second project, we are using fly genetics to uncover tissue-specific regulators of cellular growth. Flies, like humans, show allometric growth in which different organs and tissues grow at different rates relative to each other. The larval tracheal system is an excellent model to uncover these tissue-specific mechanisms of growth since it undergoes allometric growth and can be easily visualized in living animals. Through genetic screens we have identified eight genes that specifically alter tracheal growth relative to overall organismal growth, including both positive and negative regulators of growth. Our current project is aimed at understanding how these genes interact with each other to regulate tracheal growth, and to place these genes within the context of overall cellular growth pathways including the insulin and hippo signaling pathways.
- Velasquez, S., Abrham, K., Burnett, T., Chapin, B., Hendry, W., Leung, S., Madden, M., Rider, V., Stanford, J., Ward, R. E. and Chapes, S. 2018. The K-INBRE symposium: a 10-institution collaboration to improve undergraduate education. Advances in Physiology Education 42:104-110.
- Hanauer, D., Graham, M., SEA-PHAGES, Betancur, L., Bobrownicki, A., Cresawn, S., Garlena, R., Jacobs-Sera, D., Kaufman, N., Pope, W., Russell, D., Jacobs, W, Sivanathan, V., Asai, D, and Hatfull, G. 2017. An inclusive research-education community (iREC): Impact of the SEA-PHAGES program on research outcomes and student learning. Proceedings of the National Academy of Sciences, USA. 114:13531-13536.
- Hall, S. and Ward, R. E. 2016. Septate junction proteins play essential roles in morphogenesis throughout embryonic development in Drosophila. G3 (Genes/Genomes/Genetics) 6:2375-2384.
- Hall, S., Bone, C., Oshima, K., Zhang, L., McGraw, M., Lucas, B., Fehon, R. G. and Ward, R. E. 2014. Macroglobulin complement-related encodes a protein required for septate junction organization and paracellular barrier function in Drosophila. Development 141:889-898.
- Zhang, L. and Ward, R.E. Distinct Tissue Distributions and Subcellular Localizations of Differentially Phosphorylated Forms of the Myosin Regulatory Light Chain in Drosophila. Gene Expression Patterns 11:93-104.
- 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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