Collaborative Research: RUI: Convergent extension in a dynamically patterned epithelium

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For an embryo to develop from a fertilized egg into an adult, cells must elongate in a coordinated and orderly manner. Elongation is required for processes as basic as extending the body axis or as specific as growing the tips of tubules inside of kidneys. This research will examine the process of elongation in the flour beetle, Tribolium, throughout the time that the embryo is forming the repeated parts, called segments, which make up its anterior/posterior body axis. Although an apparently seamless process, previous work showed that segmentation slows down, then speeds up as the body elongates. Corresponding to this switch in rate, cells behave differently during early and late elongation stages. This work will build on those preliminary observations and, first, carefully describe the switch in how clusters of cells elongate and, second, investigate how it is controlled. This kind of discontinuity or switch in tissue elongation in a progressively elongating body axis is unusual and likely to provide insight into novel mechanisms of elongation. The research is a collaborative effort between a type 1 research university and a teaching college. A major impact of this work is to rigorously train undergraduates in interdisciplinary research, combining computer modeling of elongation with hands-on experimental manipulations of the beetle embryo. Undergraduates from the teaching college are linked to the research institution through both on-site visits and extensive online interactions. The hypothesis underlying this work is that the elongating Tribolium embryo represents a tissue that transitions between two mechanisms of convergent extension during early and late stages of embryo elongation. Based on preliminary data, a model of elongation in Tribolium is proposed in which anterior cells undergo ordered intercalation analogous to what is known in Drosophila embryo extension, while posterior cells move in a less orderly fashion relative to neighbors, directed by tissue-level boundaries in the elongating posterior. The work integrates experimental approaches with computational models to test these hypotheses. It combines live imaging of mutant embryos, that differentially affect the alternate models of elongation, with in silico modeling to provide mechanistic insights into Tribolium elongation. This research highlights Tribolium as a new model of elongation. It will develop a basic understanding of the unique genetic and cellular mechanisms that contribute to the discontinuous changes in tissue elongation in Tribolium's progressively elongating body axis. The proposed dynamic feedback between computational models and experiments will improve understanding of how upstream regulatory networks translate into discrete cell behaviors shaping morphogenesis. This work will also allow comparisons to the well-studied insect model, Drosophila, as well as vertebrates, which also elongate progressively. Such comparisons can identify variable versus conserved mechanisms of elongation, providing information about the evolution of fundamental processes that drive morphogenesis. Additionally, the project will generate RNA Seq data, genetic tools, and models of embryo and tissue elongation useful to the community at large.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.