Botryllus as a model organism

Botryllus is a colonial tunicate, a marine chordate that straddles the vertebrate/invertebrate divide and grows in shallow waters throughout the world. Botryllus begins its life as a swimming tadpole larva, with chordate features such as a notochord and dorsal, hollow nerve tube, which later settles and metamorphoses into an invertebrate adult body plan. The adult body, called a zooid, has a complex morphology, including a heart, GI tract, central and peripheral nervous system, and a germline. In addition, Botryllus belongs to a subset of tunicates that are colonial, and grow by a repetitive asexual process in which entire bodies, including all somatic and germline tissues, are regenerated de novo. This results in a colony of genetically identical zooids, which are interconnected by a large, extracorporeal vascular network, and arrange themselves into star-shaped groups called systems. Each zooid is an independent body, and inviduals and entire systems be separated from the colony (called subcloning) and will continue to grow. Thus we can have multiple independent pieces of a single genotype, which allows us to carry out studies not possible in other model organisms, for example, to repeatedly experiment on an individual as it ages.

Botryllus is lab-reared and besides its ability to regenerate, has many unique biological features, including a natural transplantation reaction reminiscent of vertebrate MHC-based allorecognition, germline stem cells with a genetically determined competitive phenotype, and an unusual aging phenotype called non-random senescence. As a sessile, transparent organism that grows on a glass slide, it can be easily live imaged, and many anatomical features, such as a large, extracorporeal vascular bed, provide unparalleled accessibility to tissues such as blood vessels that are not possible in other models. Other features of interest include a surgically induced and reversible situs inversus in the developing bud, a novel regenerative pathway called vascular budding that appears to be analogous to teratoma formation, and an inducible metabolic competition called resorption. Allorecognition responses even extend into settlement behavior of the larvae, which in turn has both evolutionary and ecological consequences. The sessile and colonial nature of Botryllus also allows us to do experiments in the lab and field using the same individual, simultaneously. Finally, Botryllus is a basal chordate, and 80% of the genes in the sequenced genome have vertebrate homologs, but the genome is far less redundant, allowing us to rapidly dissect gene function.

However, what is truly remarkable about Botryllus is the integration of these biological features: allorecognition responses create a vascular parabiosis that parasitic stem cells used to naturally transplant between individuals and contribute to asexual development. This interaction had implications that range from the cellular and molecular mechanisms of self/non-self recognition and stem cell biology (e.g. homing, self-renewal, differentiation) to the evolutionary forces that create and maintain polymorphic allorecognition systems (e.g., parasitic stem cells and transmissible cancers) that F.M. Burnet had hypothesized about over 50 years ago, and even to aging, as allogeneic interactions and stem cell transplantation often occurs between juvenile and adults. While our lab is primarily focused on molecular mechanistic studies, the biology of Botryllus puts these results into a larger context: not only can we dissect how an allorecognition response works, but we can empirically study why it exists in the first place.

Researchers

Delany Rodriguez

Characterization of the mechanisms underlying age-related functional and morphological changes in  the vasculature of the invertebrate chordate Botryllus schlosseri.

Shane Nourizadeh

My work focuses on injury-induced regeneration in two marine invertebrates, Botryllus schlosseri and Botrylloides diagensis. I've discovered that these closely related tunicate species have disparate mechanisms for injury recovery: one depends on ectopic tissue development and the other on blood borne stem cells. Currently looking into the stem-cell mediated process to temporaily quantify conserved molecular pathways, including Wnt and Notch, during the healing response. My overall aim is to understand how cell-to-cell signaling is used to coordinate early regeneration niche formation.