title: Genetics of extracellular matrix remodeling during organ growth using the Caenorhabditis elegans pharynx model.
abstract: The organs of animal embryos are typically covered with an extracellular matrix (ECM) that must be carefully remodeled as these organs enlarge during post-embryonic growth; otherwise, their shape and functions may be compromised. We previously described the twisting of the Caenorhabditis elegans pharynx (here called the Twp phenotype) as a quantitative mutant phenotype that worsens as that organ enlarges during growth. Mutations previously known to cause pharyngeal twist affect membrane proteins with large extracellular domains (DIG-1 and SAX-7), as well as a C. elegans septin (UNC-61). Here we show that two novel alleles of the C. elegans papilin gene, mig-6(et4) and mig-6(sa580), can also cause the Twp phenotype. We also show that overexpression of the ADAMTS protease gene mig-17 can suppress the pharyngeal twist in mig-6 mutants and identify several alleles of other ECM-related genes that can cause or influence the Twp phenotype, including alleles of fibulin (fbl-1), perlecan (unc-52), collagens (cle-1, dpy-7), laminins (lam-1, lam-3), one ADAM protease (sup-17), and one ADAMTS protease (adt-1). The Twp phenotype in C. elegans is easily monitored using light microscopy, is quantitative via measurements of the torsion angle, and reveals that ECM components, metalloproteinases, and ECM attachment molecules are important for this organ to retain its correct shape during post-embryonic growth. The Twp phenotype is therefore a promising experimental system to study ECM remodeling and diseases.
authors.affiliation: Department of Cell and Molecular Biology, University of Gothenburg, S-405 30 Gothenburg, Sweden.
authors.forename: Gholamali
authors.initials: G
authors.lastname: Jafari
authors.forename: Jan
authors.initials: J
authors.lastname: Burghoorn
authors.forename: Takehiro
authors.initials: T
authors.lastname: Kawano
authors.forename: Manoj
authors.initials: M
authors.lastname: Mathew
authors.forename: Catarina
authors.initials: C
authors.lastname: Mörck
authors.forename: Claes
authors.initials: C
authors.lastname: Axäng
authors.forename: Michael
authors.initials: M
authors.lastname: Ailion
authors.forename: James H
authors.initials: JH
authors.lastname: Thomas
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Culotti
authors.forename: Peter
authors.initials: P
authors.lastname: Swoboda
authors.forename: Marc
authors.initials: M
authors.lastname: Pilon
mesh_terms: D000483:Alleles; D000818:Animals; D001485:Basement Membrane / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000254:growth & development*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D002874:Chromosome Mapping; D019483:Disintegrins / Q000378:metabolism; D005109:Extracellular Matrix / Q000235:genetics* / Q000378:metabolism; D055785:Gene Knockdown Techniques; D017238:Genes, Helminth / Q000235:genetics; D005838:Genotype; D008666:Metalloendopeptidases / Q000378:metabolism; D023421:Models, Animal; D009154:Mutation / Q000235:genetics; D009928:Organ Specificity / Q000235:genetics; D010614:Pharynx / Q000002:abnormalities / Q000201:enzymology / Q000254:growth & development* / Q000473:pathology; D010641:Phenotype; D034622:RNA Interference; D014102:Torsion Abnormality / Q000473:pathology
chemical_list: D029742:Caenorhabditis elegans Proteins; D019483:Disintegrins; C410348:MIG-17 protein, C elegans; D008666:Metalloendopeptidases
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