Determining the Roles of SMOC-1 in Transforming Growth Factor Beta (TGF-ß) Signaling in C. elegans

Science Center, Bent Corridor

The bone morphogenetic protein (BMP) pathway is a highly conserved signaling pathway with many important functions. Mutations in the genes functioning in this pathway can give rise to heart and skeletal problems as well as certain cancers in humans. In C. elegans, the BMP pathway regulates several systems including body size, which is the metric I am using to determine how a newly identified secreted protein, SMOC-1, functions in the BMP pathway. smoc-1 null mutants (smoc-1(0)) are smaller, while worms over-expressing smoc-1 (smoc-1(OE)) are longer, than wild-type worms. I have generated double mutants between smoc-1(OE) and null mutations in genes dbl-1, sma-3, lon-2 and lon-1, which encode the ligand, a cytoplasmic transducer R-Smad protein, a negative regulator glypican and a target of the pathway, respectively. I have measured the body lengths of the double mutants and compared their lengths with the corresponding single mutants and with wildtype animals. My results suggest that SMOC-1 functions upstream of the ligand DBL-1 and the negative modulator LON-2 in the BMP pathway. To determine if SMOC-1 is specifically involved in modulating the BMP pathway, I am also testing whether SMOC-1 is involved in a pathway closely related to the BMP pathway, the dauer TGF-β pathway. This is achieved by generating double mutants between smoc-1 null mutations and null mutations in daf-7 and daf-1, which encode the ligand and type I receptor of the dauer pathway, respectively, and assessing the dauer phenotype of the resulting double mutants. Results from my experiments will help contribute to our understanding of the functions of SMOC-1 in vivo.