bioRxiv ScienceSearch

Biology subjects

Sigg, M. A.

Publications and source records attributed to Sigg, M. A..

2 recordsLinked to original sources

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

The mechanisms underlying multicellular development in the animal stem lineage may be reconstructed through the study of choanoflagellates, the closest living relatives of animals. To determine the genetic underpinnings of multicellularity in the emerging model choanoflagellate S. rosetta, we performed a screen for mutants with defects in multicellular rosette development. In two of the mutants, Jumble and Couscous, single cells failed to develop into orderly rosettes but instead aggregated promiscuously into amorphous clumps of cells. Both mutants mapped to lesions in genes encoding glycosyltransferases and the mutations perturbed glycosylation patterns in the extracellular matrix (ECM). In animals, glycosyltransferases transfer activated sugars to donor molecules and thereby sculpt the polysaccharide-rich ECM, regulate integrin and cadherin activity, and, when disrupted, contribute to tumorigenesis. The finding that glycosyltransferases promote proper rosette development and prevent cell aggregation in S. rosetta suggests a pre-metazoan role for glycosyltransferases in regulating development and preventing abnormal tumor-like multicellularity.\n\nIMPACT STATEMENTA genetic screen reveals that glycosyltransferases are required for proper rosette development and the prevention of cell clumping in one of the closest living relatives of animals, the choanoflagellate S. rosetta.

genetics

Evolutionary proteomics uncovers ciliary signaling components

Cilia are organelles specialized for movement and signaling. To infer when during animal evolution signaling pathways became associated with cilia, we characterized the proteomes of cilia from three organisms: sea urchins, sea anemones and choanoflagellates. From these ciliomes, we identified 437 high confidence ciliary candidate proteins conserved in mammals, including known regulators of Hh, GPCR and TRP channel signaling. The phylogenetic profiles of their ciliary association indicate that the Hh and GPCR pathways were linked to cilia before the origin of bilateria and TRP channels before the origin of animals. We demonstrated that some of the candidates not previously implicated in ciliary biology localized to cilia and further investigated ENKUR, a TRP channel-interacting protein that we identified in the cilia of all three organisms. In animals, ENKUR is expressed by cells with motile cilia, ENKUR localizes to cilia in diverse organisms and, in both Xenopus laevis and mice, ENKUR is required for patterning the left/right axis. Moreover, mutation of ENKUR causes situs inversus in humans. Thus, proteomic profiling of cilia from diverse eukaryotes defines a conserved ciliary proteome, reveals ancient connections to Hh, GPCR and TRP channel signaling, and uncovers a novel ciliary protein that controls vertebrate development and human disease.

evolutionary biology