Developing a new chordate model for stem cell biology and regeneration

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ABSTRACT The goal of this grant is to adapt contemporary single cell resolution and genomic manipulation tools to utilize the unique regenerative biology of the colonial ascidian species, Botryllus schlosseri. The FOA we are responding to from ORIP has as its stated goal to create new and innovative models for stem cell biology and regeneration, and Botryllus has a proven track record of innovative studies and a wealth of biology that will be made accessible with these new tools. Ascidians are chordates, and considered to be the closest living relatives to the vertebrates. Species such as Ciona have become powerful models in dissecting early steps in chordate embryogenesis due to their relative simplicity and rapid development, and share many chordate-specific features, including early mechanisms underlying cell specification, as well as clonal origins of multiple tissues. In addition to this close phylogenetic relationship, a subset of ascidian species are colonial, and grow, not by increasing in size, but via a process of regeneration- whereby entire bodies- including all cardiovascular, nervous, endocrine and germline tissues- are regenerated, and in Botryllus this occurs every week in a synchronized fashion, providing a novel model to study regeneration of all major organ systems in a chordate. Colonial ascidians are the only chordates with the ability to regenerate every tissue and organ in their body and unique life history characteristics make Botryllus a potentially outstanding model for these studies.