The transition from unicellularity to multicellularity initiated the evolution of animals, one of the most important and least understood events in the history of life. From the study of traditional research models like flies and mice we have learned that myriad mechanisms have evolved to meet the demands of the multicellular condition, such as cell-cell attachment, cell-cell communication, and the ability to distinguish one?s own cells from those of other organisms (self-recognition). The goal of this project is to broaden this body of research to include sponges, which are hundreds of millions of years divergent from all other animals. To the extent that sponges and any other animal use the same molecular mechanisms for mediating cell-cell interactions, unifying design principles, both common and ancestral to all animals, may be inferred from the study of sponges. The available evidence indicates that sponge cell-attachment and self-recognition depend upon a molecular complex termed the ?Aggregation Factor? that is not found in other animals. However, the composition of the Aggregation Factor is incompletely known; it is unclear whether all sponges produce this complex; and it is entirely unknown how it relates to molecular systems in other animals. The goal of the proposed research is to understand the role of aggregation factor and other associated proteins in aggregation, adhesion, and communication. Beyond the immediate scientific goals, the impact of this research will be extended through: 1) development of a citizen science program to document the diversity and distribution of freshwater sponges in North America, 2) development of an open-access repository of newly developed tools and techniques for cultivation and experimental manipulation of sponges in the laboratory, and e) training of students.
The long-held view is that, unlike any other animal, sponge tissues are loosely organized, with cells embedded in a common extracellular matrix composed, in part, of the Aggregation Factor (AF). The AF is thought to cross-link adjacent cells and to serve in self/non- self-recognition. But, an important caveat to this view is that the Aggregation Factor has predominantly been studied in vitro (in cell aggregation studies), whereas more recent studies of intact tissues have revealed an important role for cadherin- and integrin-based cell junctions, much like epithelial tissues in other animals. The proposed research will use 1) proteomic methods to comprehensively determine AF composition in diverse sponge lineages, 2) immunostaining to determine the relative distribution of the AF and cell junctions in tissues, 3) co- immunoprecipitation and pull-downs to test for endogenous interactions between the AF with cell junctions, and 4) small molecules and peptides to perturb integrin signaling in AF-mediated processes of cell aggregation and self-recognition. Conceptually, these results will clarify how multicellular integrity is maintained in sponges and increase the understanding of the evolutionary origin of multicellular integrity and tissue organization in animals.
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.
