Symmetry Breaking in Cell Assemblies

Summary Tissue wide patterning is integral to robust development in multicellular organisms, requiring individual cells to generate polarity axes and coordinate this information in space and time. In order to establish cell polarity individual cells must first `break symmetry'. Imaging symmetry breaking in vivo suggests this is not a stochastic process, instead, symmetry breaking events are coordinated with in tissues and interconnected across the embryo. Using the C. elegans embryo, I will take a systems level approach to identify patterns of symmetry breaking events in the embryo that underlie synchronized, reproducible cell polarization needed for proper development. The Feldman lab has developed the C. elegans intestine as a tractable model to define cell- and tissue-level symmetry breaking events in the in vivo context of the developing embryo. The first cellular-level asymmetry we observe is the formation of `local polarity complexes' (LPCs). These macromolecular assemblies subsequently move coordinately to seed and establish the future apical surface, defining tissue-level asymmetry. In the proposed experiments, I will probe molecular assemblies to identify conserved mechanisms of polarity complex formation (aims 1 & 2) and ask if mechanical inputs are upstream of directed symmetry breaking in epithelia in vivo (aim 3). The overarching goal of this proposal is to identify where asymmetric information comes from to inform polarity programs in developing epithelia. Together these aims will inform core mechanisms of cell polarity establishment that are essential for organismal development and are key to maintaining healthy epithelia and preventing disruption of polarity programs that underlie disease states such as congenital malformations and tumorigenesis.