Identification of genetic interactions between the DBL-1/BMP-like pathway and other body size-associated genes in Caenorhabditis elegans

Bone morphogenetic protein (BMP) signaling pathways are conserved in animals and are used to control many developmental and homeostatic processes, including cell size and extracellular matrix remodeling. To identify novel regulators of BMP signaling, we performed a forward genetic screen in C. elegans for genes involved in body size regulation, a trait under the control of BMP member DBL-1. We isolated mutations that suppress the long phenotype of lon-2, a gene that encodes a negative regulator that sequesters DBL-1. We effectively isolated alleles of several core components of the DBL-1 pathway, demonstrating the efficacy of the screen. We found additional alleles of previously identified but uncloned body size genes. We also identified widespread involvement of extracellular matrix proteins in the DBL-1 regulation of body size. We characterized interactions between the DBL-1 pathway and extracellular matrix genes and other genes that affect body morphology. We discovered that loss of some of these genes affects DBL-1 pathway signaling. Two prominent cuticular collagens, DPY-2 and DPY-9, have stage-specific effects on DBL-1 signaling. We propose a model in which DBL-1 controls multiple body size factors, and the DBL-1 pathway is itself affected by novel regulators.