The Role of Mechanical Interactions in Tissue Formation and Body Axis Specification

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Despite their remarkable diversity, all animals begin as a single, fertilized egg. How patterns are established from an initially near uniform system, the egg, is a fundamental question in biology. Mechanical interactions between cells and their environment are thought to play an important role in tissue and axis formation, but this has been difficult to dissect experimentally because of the complexity of developing embryos. The award will investigate the role of mechanical forces in the formation of body form of the Hydra from a solution of separated cells. How the tension at the cell surface and the stiffness of layers of tissue fibers that the cells secrete change how the animal structure develops also will be measured. This award supports fundamental research aimed at studying a simple animal that can regenerate its body after dissociation into individual cells. The core mechanical mechanisms of cell-cell interactions during body plan development are universal during early development. Understanding how these mechanisms work in a simple organism will lead to insight into these mechanisms in more complex beings. This research may reveal general guiding principles for tissue assembly and organ formation and thus has implications for medicine in the context of engineering tissues and organs for transplantation. Understanding how an organism can emerge from an aggregation of cells sparks human imagination. Therefore this project will offer exciting research opportunities for undergraduate and graduate students. The interdisciplinary nature of the project requires the application of tools from physics, biology, engineering, and computer science, and thus will enable students from diverse backgrounds to make significant contributions.It is experimentally challenging to dissect the mechanical interactions involved in animal development. A novel system which promises to allow such a dissection is the freshwater polyp Hydra, which self-organizes and regenerates after dissociation into a suspension of single cells. Because of this remarkable ability and its structural simplicity, regenerating Hydra aggregates are fully accessible to quantitative measurements and controlled perturbations while providing an in vivo environment that makes the measurements meaningful. This research will elucidate how tissue formation occurs from a cell suspension and determine the mechanisms that lead to body axis specification. For both processes, the research team will apply a multiscale approach from the molecular to the organismal level and test the importance of mechanical interactions using physical measurements, chemical manipulations, visualization of gene expression using transgenic animals and immunohistochemistry, and fluorescent time-lapse microscopy. This study will provide insight into how macroscopic organism-level patterning emerges from interactions on the cellular level.