Genetic interactions between the DBL-1/BMP-like pathway and dpy body size-associated genes in Caenorhabditis elegans.

Abstract

Bone morphogenetic protein (BMP) signaling pathways control many developmental and homeostatic processes, including cell size and extracellular matrix remodeling. An understanding of how this pathway itself is controlled remains incomplete. To identify novel regulators of BMP signaling, we performed a forward genetic screen in Caenorhabditis 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. This screen was effective because we 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. Our screen also identified widespread involvement of extracellular matrix proteins in DBL-1 regulation of body size. We characterized interactions between the DBL-1 pathway and extracellular matrix and other genes that affect body morphology. We discovered that loss of some of these genes affects the DBL-1 pathway, and we provide evidence that DBL-1 signaling affects many molecular and cellular processes associated with body size. We propose a model in which multiple body size factors are controlled by signaling through the DBL-1 pathway and by DBL-1–independent processes.