Muravin, Ines et al. (2021) International Worm Meeting "Elucidating the role of SUP-17/ADAM10 in the BMP signaling pathway in C. elegans"

Nzessi, Anthony, Liu, Zhiyu, Liu, Jun, Muravin, Ines, Wang, Lin

[International Worm Meeting, 2021]

Bone Morphogenetic Protein (BMP) signaling is a highly conserved cascade that is involved in many essential biological events across metazoans, like cell migration, proliferation, and differentiation. Numerous hereditary disorders ranging from cancer to cardiovascular disease can arise in humans when this pathway malfunctions. Consequently, gaining a better understanding of how this pathway is tightly regulated could help us to address and, ultimately, treat these medical conditions. In C. elegans, the BMP pathway is known to regulate body size, postembryonic mesoderm development, and several other developmental processes. Multiple factors have been identified to be involved in modulating BMP signaling. One such factor is the ADAM (a disintegrin and metalloprotease) protease SUP-17, whose mammalian ortholog is ADAM10. SUP-17/ADAM10 is a single-pass transmembrane protein that plays a fundamental role in ectodomain shedding, a post-translational modification where either a transmembrane or membrane-associated protein is cleaved at the extracellular domain through juxta-membrane processing. Our research aims to elucidate the role of SUP-17/ADAM10 by identifying its substrate(s) in BMP signaling. Towards this goal, we have used the CRISPR/Cas9 technique to tag multiple known transmembrane and membrane-associated proteins involved in BMP signaling with GFP and FLAG. We are conducting western blot analyses on wild-type and sup-17 mutant worms carrying each of these tagged proteins. We also plan to use an unbiased proteomic approach to identify SUP-17/ADAM10 substrate(s) in BMP signaling. Results from these studies will shed light on how SUP-17/ADAM10 functions to regulate BMP signaling.

Fujita, Masashi et al. (2010) C. elegans: Development and Gene Expression, EMBL, Heidelberg, Germany "Surface tension is the primary determinant of cell shape in the two-cell stage embryo"

Fujita, Masashi, Onami, Shuichi

[C. elegans: Development and Gene Expression, EMBL, Heidelberg, Germany, 2010]

The shape of cells in tissues and embryos bears a striking resemblance to soap bubbles. Since surface tension governs the shape of soap bubbles, it has also been considered as the major determinant of the cell shape. However, evidence of this hypothesissurface tension modelbeyond the superficial similarity is still scarce. The two-cell stage embryo, which might be the simplest cell aggregate, would serve as an ideal system for a rigorous test of the model. In that stage, the larger blastomere (AB) always bulges toward the smaller one (P 1 ). This is intriguing because soap bubbles behave in the opposite way. We found that the surface tension model is not only able to explain this phenomenon but also consistent with its molecular and physical properties. Cytoskeletal inhibitors and a ts mutant showed importan ce of actomyosin on the bulge formation. NMY-2::GFP showed cortical localization and was significantly more abundant on the cortex of AB than that of P 1 . A UV-irradiation experiment confirmed the bulges dependency on AB. These results indicate that the driving force of the bulge formation is a stronger cortical contractility of AB. Computer simulation showed that higher surface tension of AB can form a bulge. Moreover, the simulated shape had close resemblance to a real embryo. Essential predictions of the model were experimentally tested. It predicts that the immediate cause of the bulge is higher pressure inside AB. This prediction was verified by cytoplasmic stream after laser fusion of the cells. Another important prediction is shrinkage of the surface area of AB, which reflects the cortical contractility. This was also confirmed by quantification of the cell geometry. These evidences strongly support the idea that surface tension is the primary factor that determ ines the cell shape of embryo.