title: Regulation of extracellular matrix organization by BMP signaling in Caenorhabditis elegans.
abstract: In mammals, Bone Morphogenetic Protein (BMP) pathway signaling is important for the growth and homeostasis of extracellular matrix, including basement membrane remodeling, scarring, and bone growth. A conserved BMP member in Caenorhabditis elegans, DBL-1, regulates body length in a dose-sensitive manner. Loss of DBL-1 pathway signaling also results in increased anesthetic sensitivity. However, the physiological basis of these pleiotropic phenotypes is largely unknown. We created a DBL-1 over-expressing strain and show that sensitivity to anesthetics is inversely related to the dose of DBL-1. Using pharmacological, genetic analyses, and a novel dye permeability assay for live, microwave-treated animals, we confirm that DBL-1 is required for the barrier function of the cuticle, a specialized extracellular matrix. We show that DBL-1 signaling is required to prevent animals from forming tail-entangled aggregates in liquid. Stripping lipids off the surface of wild-type animals recapitulates this phenotype. Finally, we find that DBL-1 signaling affects ultrastructure of the nematode cuticle in a dose-dependent manner, as surface lipid content and cuticular organization are disrupted in animals with genetically altered DBL-1 levels. We propose that the lipid layer coating the nematode cuticle normally prevents tail entanglement, and that reduction of this layer by loss of DBL-1 signaling promotes aggregation. This work provides a physiological mechanism that unites the DBL-1 signaling pathway roles of not only body size regulation and drug responsiveness, but also the novel Hoechst 33342 staining and aggregation phenotypes, through barrier function, content, and organization of the cuticle.
authors.affiliation: Department of Molecular and Cellular Medicine, Texas A&M Health Science Center College of Medicine, College Station, Texas, United States of America; Interdisciplinary Program in Genetics, Texas A&M University, College Station, Texas, United States of America.
authors.forename: Robbie D
authors.initials: RD
authors.lastname: Schultz
authors.affiliation: Department of Molecular and Cellular Medicine, Texas A&M Health Science Center College of Medicine, College Station, Texas, United States of America.
authors.forename: Emily E
authors.initials: EE
authors.lastname: Bennett
authors.affiliation: Microscopy & Imaging Center, Texas A&M University, College Station, Texas, United States of America.
authors.forename: E Ann
authors.initials: EA
authors.lastname: Ellis
authors.affiliation: Department of Molecular and Cellular Medicine, Texas A&M Health Science Center College of Medicine, College Station, Texas, United States of America; Interdisciplinary Program in Genetics, Texas A&M University, College Station, Texas, United States of America.
authors.forename: Tina L
authors.initials: TL
authors.lastname: Gumienny
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism*; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
chemical_list: D019485:Bone Morphogenetic Proteins; D029742:Caenorhabditis elegans Proteins; C117509:Dbl-1 protein, C elegans; D009479:Neuropeptides; D016212:Transforming Growth Factor beta