Project Summary The broad goal of this work is to understand how embryos coordinate the fusion and separation of epithelial sheets during early development. A primary example of this occurs during neural tube closure when the lateral edges of the neural primordium (the neural folds) meet at the midline and fuse to separate a closed neural tube from a continuous overlying epidermis. This process is known as zippering because it proceeds directionally from initial points along the anterior-‐posterior axis from initial points of contact. Zippering is common to many forms of epithelial fusion, but how it works is poorly understood. A key challenge is to understand how the forces are produced that pull the neural folds together and drive the zipper forward and how these forces are controlled in space and time to achieve a We will address these challenges using the invertebrate chordate Ciona intestinalis as a model system. Ciona offers a uniquely tractable opportunity to study a very simple form of epithelial zippering and neural tube closure involving very few cells with well-‐developed tools for molecular genetic manipulation, transgenesis and high-‐speed live imaging. In recent work, we showed that zippering is powered by a dynamic sequence of actomyosin-‐ dependent junction contractions that sweeps from posterior to anterior along the lateral edges of the neural plate. We will use a highly interdisciplinary combination of quantitative imaging, experimental manipulations and predictive modeling to ask the following questions: (1) How is this wave of contraction controlled through cell-‐cell signaling along the Neural/Epidermal boundary and between neural folds across the midline? (2) What are the signaling pathways that mediate this control? (3) How are local signaling, force production and tissue remodeling integrated to create a self-‐propagating wave of junction contraction and tissue fusion across the embryo? Because many of the molecules that mediate cell-‐cell signaling and force production are highly conserved across the metazoa, our work will have direct relevance to understanding neural tube closure and tissue fusion generally in higher chordates, and it will provide new insights into how failures in this process can lead to birth defects in humans.