UCSF

The proper organization and coordination of cells is essential to the integrity and function of tissues, organs, and multicellular organisms. While diverse organs and organisms have been used to study these foundational principles, the shear structural and compositional complexity of many in vivo experimental models raises numerous challenges to dissecting the cellular mechanisms underlying their formation and function. Conversely, in vitro models, despite limiting structural complexity, frequently fail to recapitulate the complete physiology of the organs from which they are derived. To ameliorate these tradeoffs, we exploited the anatomical simplicity and extraordinary regenerative capacity of the basal metazoan Hydra vulgaris to probe the mechanisms of tissue patterning and coordinated cellular physiology. In Chapter 2, we apply live microscopy and physical cellular manipulation to investigate a decades-old observation in which a disordered aggregate of Hydra cells sorts into inner and outer epithelial compartments, a prerequisite to regenerating a functional body plan. We show that differences in the rates of epithelialization between two primary cell types give rise to the bilayered structure of the intact animal. In Chapter 3, we investigate the function of these assembled tissues. Specifically, through the identification and dissection of a fluid engulfment phenomenon known as macropinocytosis, we reveal a role for tissue mechanics in regulating fluid uptake and membrane recycling in homeostatic Hydra epithelia. Together, these studies illustrate how the emergent properties of cell collectives, such as cell polarity and tissue mechanics, can contribute to the structure and function of living animals.