UC Santa Barbara

The morphogenesis of cells and tissues involves an intricate coordination of physical and biological processes. In this thesis, we focus on the unidirectional elongation of cells and tissues. We use budding yeast mating projection growth and the axis elongation of zebrafish as our motivating examples of cell elongation and tissue elongation respectively. Both require a fluid to solid transition in the growing structure for elongation to occur.

The mating projection growth of yeast cells display polarized, unidirectional growth. It is unclear how information about the mechanical state of the wall is relayed to the molecular processes building it, thereby enabling the coordination of cell wall expansion and assembly during morphogenesis. Combining theoretical and experimental approaches, we show that a mechanical feedback coordinating cell wall assembly and expansion is essential to sustain mating projection growth in budding yeast (Saccharomyces cerevisiae). Our theoretical results indicate that the mechanical feedback provided by the Cell Wall Integrity pathway, with cell wall stress sensors Wsc1 and Mid2 increasingly activating membrane-localized cell wall synthases Fks1/2 upon faster cell wall expansion, stabilizes mating projection growth without affecting cell shape. Experimental perturbation of the osmotic pressure and cell wall mechanics, as well as compromising the mechanical feedback through genetic deletion of the stress sensors, leads to cellular phenotypes that support the theoretical predictions.

The mechanisms that maintain continued polarization to the growth region during mating projection formation, and the subsequent change in geometry from a spherical cell, remain unknown. We theoretically show that a genetically-encoded mechanical feedback relaying information about the cell’s geometry is sufficient to ensure that key polarity molecules (e.g., Cdc42) remain localized to the site of growth. Interestingly, we find that a common feedback mechanism, connecting the physics/geometry of the cell wall to the cellular molecular machinery, can both stabilize cell growth and maintain polarity.

Tissue morphogenesis requires the successful translation of molecular information to the physical fields that shape tissues into their functional morphologies. While regional control of cellular forces or cell proliferation has been assumed to be the main contributor to shaping tissues, it has been recently shown that the elongation of the body axis entails a fluid-to-solid transition in the state of the tissue. Here we theoretically study how the regional control of the fluid and solid states controls morphogenesis of the extending body axis and how morphogenetic flows emerge from the underlying inhomogeneities in physical fields. We theoretically describe from first principles the process of tissue morphogenesis accounting for contact inhibition of proliferation, a mechanical feedback preventing cell proliferation when tissue pressure is high, and show that both the existence of a fluid-to-solid transition and the tissue surface tension determine the shape of the tissue and its ability to elongate unidirectionally. Our results indicate the existence of counter-rotating vortices in the tissue that arise from the interplay between tissue rigidification and growth. Posterior tissues are found to globally push on anterior tissues to support elongation, but stresses in the tissue can display regions of both pulling and pushing forces. These results help explain how the regional fluidization of the posterior tissues drives posterior body elongation in vertebrates and the formation of complex morphogenetic flows.