Biophysical mechanisms underlying Drosophila renal tubule morphogenesis

PROJECT SUMMARY/ABSTRACT Organs have specific three-dimensional (3D) architectures that are essential for their physiological functions. By integrating chemical and physical inputs, cells build and sculpt complex 3D tissue shapes. Understanding the molecular and physical architectural rules governing the formation of our organs could offer insights into how deviations from these rules contribute to human diseases. Despite the prevalence of looped epithelial tubular structures throughout our organs we lack fundamental knowledge of the strategies cells use to build these complex tissue structures. The goal of my research program is to understand the emergent properties cells use to sculpt organ shapes. To achieve this goal, we use the developing Drosophila renal system which involves the generation and extension of epithelial tubes that bend and loop in 3D in a stereotypic manner. This experimentally tractable system is ideal to identify the parameters that generate complex tissue forms while keeping the cells in an in vivo context. Here we will couple our ability to both visualize and perturb key drivers of tissue morphogenesis to determine how these drivers influence cell shape, collective cell behavior, and ultimately organ form. In this project, we will focus on the following questions: (1) How is contractile machinery in cells organized to coordinate tissue-scale behavior? and (2) How do cells coordinate to dynamically pack (and repack) in a tissue that is changing shape? To address these questions, we are developing techniques to visualize, track, and quantify both the 3D cell behaviors and machineries that drive these tissue movements in vivo. We will build on work by myself and others to understand the molecular and physical principles cells use to bend and extend epithelial sheets to reveal how cells drive the formation of looped epithelial tubes. Identifying these general principles of tissue morphogenesis will provide insight into how dysregulation of these rules leads to human disease and provide opportunities to develop novel therapeutic strategies to treat them.