"Topological transitions of epithelial tissues"
This event is part of the Biophysics Seminars. 12:30PM.
The epithelium is a fundamental tissue architecture that lines the outer surfaces of many organs and inner cavities within them. While past studies have demonstrated how local differences in cell mechanical properties induce epithelial folding, the question of epithelial topology has not been addressed. What are the physical conditions that determine whether an epithelium remains well connected, or transitions to a phase where the tissue divides into multiple, topologically distinct epithelia? I have developed a novel in vitro assay to address how developmental cues, cell biological mechanisms, and tissue mechanics interact to govern the topological transition of epithelial tissues. In this assay, free-floating aggregates of ~1000 mouse embryonic stem cells are differentiated into the neural lineage in medium supplemented with extracellular. Within 4 days, a continuous apical membrane domain is observed in the interior of the tissue as a result of collective cell polarization and epithelialization. Treatment with retinoic acid induces a change in epithelial topology where the apical membrane domain splits up into multiple spherical structures, which is explained as a multiple cyst phenotype. My preliminary results support a scenario where reduced lysophosphatic acid signaling, and consequently, reduced PODXL protein levels to be downstream of retinoic acid. PODXL is an apical membrane protein with a negatively charged extracellular domain, which I hypothesize to increase apical surface area. Based on these findings, I propose that epithelial topology can predicted in a physical framework similar to surfactant self-assembly.