Parallel genetic pathways contribute to epidermal structure and resistance of biomechanical force during C. elegans development

Esposito, Kyla
During development, biomechanical forces shape the embryo from an oval to an elongated cylindrical form. FBN-1 is a C. elegans zona pellucida domain protein that is synthesized and transported to the outside of the worm forming long fibers that bind to the epidermis, allowing for the maintenance of proper shape while undergoing the biomechanical pulling force of the elongating pharynx during embryogenesis. The worm FBN-1 is conserved in vertebrate fibrillin proteins in which mutations cause the disease Marfan Syndrome. The worm SYM-4 is a highly conserved protein in vertebrates and controls endocytic recycling and exocytosis in epithelia. FBN-1 and SYM-4 work in parallel pathways to enhance Pharynx-ingressed (PIN) phenotype, a larval synthetically lethal phenotype. PIN is characterized by the posterior displacement of the pharynx and buccal capsule resulting in larvae that are unable to feed. The goal of this project was to determine other genes that may be working with FBN-1 and SYM-4 to allow the epidermis to resist the biomechanical force of the pharynx as it develops. Two strains of worms were used each containing a hypomorphic allele for FBN-1 and SYM-4, respectively. An RNAi screen was performed to look for enhanced PIN in a hypersensitized SYM-4 mutant and produced 32 genes that enhanced the PIN phenotype. These enhancers were then tested in the FBN-1 background to determine which of the parallel pathways, FBN-1 or SYM-4, the gene was in.
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