Glycosyltransferase homologs prevent promiscuous cell aggregation and promote multicellular development in the choanoflagellate S. rosetta

The mechanisms underlying multicellular development in the earliest animals may be revealed through the study of the closest living relatives of animals, choanoflagellates. The emerging model choanoflagellate S. rosetta can develop from a single cell into a multicellular rosette through a process of serial cell divisions. Through a screen for rosette defect mutants, we have uncovered multiple S. rosetta mutants in which single cells fail to develop into orderly rosettes but instead aggregate promiscuously into amorphous clumps of cells. By mapping the genetic lesions underlying two of these clumping/rosette defect mutants, Jumble and Couscous, we found that both are monogenic and caused by mutations in genes encoding glycosyltransferases, enzymes that transfer activated sugars to donor molecules. These are only the second and third genes to be implicated in the regulation of multicellularity in choanoflagellates to date. Animal glycosyltransferases contribute to the production of the polysaccharide-rich glycocalyx that covers nearly all animal cells, regulate the activity of integrins and cadherins (proteins critical for development and cell-cell adhesion), and, when disrupted, can contribute to tumorigenesis. Our finding that glycosyltransferases in S. rosetta are required to prevent spurious cell adhesion in single cells and to promote proper cell adhesion during rosette development suggests a pre-metazoan role for glycosyltransferases in regulating development and preventing abnormal tumor-like multicellularity.