RoL: Coordination of collective cell migration in complex tissues

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The development of animals requires the movement of cells to create and shape tissues and organs in the embryo. Cells often cooperate with each other by moving as a united group, but how this works is unclear. This research uses the simple fruit fly model, along with genetics and live cell imaging, to probe how groups of cells come together, adapt their shapes, and move as one within a whole tissue. This project will define the way that cells move together in the tissues and organs of many animals. A broader impact will be the recruitment of college students from underrepresented groups to perform in-depth research. Workshops for 6th-8th grade and 9th-12th grade girls will use a low-cost ‘build your own’ microscope (the Foldscope) to learn about nature and science. Lastly, engineering students will design and make a device to alter the tissue and find out the impact on how cell groups move. These activities will help students get excited about biology and inspire them to become scientists or engineers.Movement is a fundamental property of life, that crosses many levels, from molecules to cells and tissues to organisms. Cell migration is fundamental to how diverse tissues and organs form and are remodeled during animal embryonic development. Migrating cells must sense, respond, and adapt to changes in the immediate tissue environment. Cells that move collectively are further challenged to stay together, communicate, respond, and adapt cooperatively as multicellular units to tissue-scale forces and signals. An integrated understanding of the mechanisms that keep cell collectives moving inside tissues is lacking. The proposed studies will fill this knowledge gap by elucidating the dynamic molecular, cytoskeletal, organellar, cellular, and tissue-level mechanisms that promote collective cell motility in complex environments. Specifically, this project uses the Drosophila border cell collective because it is a tractable model amenable to real-time live cell imaging, genetic tools, and optogenetic cellular manipulation, all within the native developing tissue. Building on previous studies, this project will uncover: (1) how the critical signaling nexus Rap1 coordinates adhesion and the cytoskeleton to keep border cells moving inside the developing tissue; (2) how nuclear deformation, along with connections to the cellular cytoskeleton, helps border cells adapt to changes in the tissue microenvironment and morphology; (3) how alterations in gene expression facilitate movement inside crowded tissues. These studies will uncover conserved mechanisms that drive and regulate collective cell movement within tissues, thus linking principles of cooperativity and adaptability in the movement of cell nuclei, single cells, collectives, tissues, and animals as a whole.This research award is funded by the Developmental Systems, Cellular Dynamics and Function, and Rules of Life Programs, all within the Biological Sciences Directorate.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.