Mechanisms underlying epithelial tube formation

Louisiana State University, Baton Rouge LA

Investigators

Abstract

Many organs in the human body, like the lungs and kidneys, are organized as a single layer of cells surrounding a tube. During organ formation, cells on a flat sheet change their shapes and positions to form a three-dimensional tube. The cellular forces driving such cell shape changes and rearrangement are generated by cytoskeletal proteins that act like motors moving along protein-based filaments. Therefore, determining the regulatory mechanisms of the cytoskeletal protein networks is essential to understanding how organs form a proper shape. Using the developing salivary glands of the fruit fly Drosophila melanogaster, this research will fill the gap in our knowledge of the signaling pathway that controls dynamic cytoskeletal networks during tube formation. A postdoctoral researcher and graduate and undergraduate students from diverse backgrounds will be trained in techniques of genetic manipulations, advanced microscopy, and biochemical and cellular assays. Scientific outreach programs, such as the Student Research Mentorship Program, will encourage local middle school students to learn about organ formation during development and promote critical thinking and testing hypotheses. Presentations to the public will be given on organ formation and human diseases linked to defects in malformed tubular organs. Contractile actomyosin structures are created or polarized in response to cell-cell signaling and regulated by localized activation of RhoA GTPase. The overall goal of this research is to define better how signaling at the cell surface by G protein-coupled receptors (GPCRs) directs RhoA function to precisely control epithelial tube formation. Conceptually, this project will 1) fill out the gap in our knowledge of the signaling pathway by identifying and characterizing unidentified salivary gland GPCRs that reorganize actomyosin networks; 2) reveal the role of new key components in activation of Rho signaling during epithelial tube formation; 3) discover the mechanisms of how GPCR-Rho signaling organizes cortical actin during tissue invagination. By combining genetics, immunohistochemistry, confocal and super-resolution imaging, timelapse live imaging, computational image analysis, and biochemical approaches, this research will help us understand how dynamic cellular behaviors result in precise changes in tubular organ formation. The resulting data, methods, and findings will be broadly distributed. This research will provide deeper insights into the molecular mechanisms underlying tubular organ formation. This project is jointly funded by the Cell Dynamics & Function Program of MCB Molecular and Cellular Biosciences, the Established Program to Stimulate Competitive Research (EPSCoR). This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.