Hildebrand, Jeffrey
(2020)
Genetic tools for identifying regulators of cell morphology.
In: Pitt Momentum Fund 2020, University of Pittsburgh, Pittsburgh, Pa.
(Unpublished)
Abstract
"Research in my lab focuses on understanding the mechanical basis of tissue morphogenesis at the cellular and molecular level. We have previously described a pathway that controls cellular architecture and, in turn, defines tissue morphology during essential developmental processes, such as formation of the vertebrate central nervous system. This pathway consists of the core proteins Shroom3, Rho-kinase, and non-muscle myosin II and functions to regulate cell morphology by regulating the assembly of contractile networks comprised of actin and myosin. We have established that this pathway is conserved in most animals and have engineered and validated a series of tools in the invertebrate model system Drosophila melanogaster. The aim of this proposal is to perform a genome wide genetic modifier screen to identify the proteins and pathways that cooperate with Shroom to define tissue architecture during development. Following the initial identification, we will determine if the vertebrate orthologs of these genes also function to regulate cell architecture. The overall objective of this project is to produce a compendium of the proteins and pathways that control tissue morphogenesis and may be relevant to human development and disease. Work from this project will be foundational for understanding the integration of signaling networks that regulate cell architecture during the formation of complex tissues and should provide the preliminary data to pursue studies in vertebrate model systems of human disease and birth defects. Additionally, the screening tools and methods described here are being used in an undergraduate authentic research course, high school outreach programs, and independent undergraduate research projects, thus indicating the potential for this work to have a positive impact on the educational missions of the University of Pittsburgh."
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