title: UNC-52/perlecan affects gonadal leader cell migrations in C. elegans hermaphrodites through alterations in growth factor signaling.
abstract: The unc-52 gene of Claenorhabditis elegans encodes a homologue of the basement membrane heparan sulfate proteoglycan perlecan. Viable alleles reduce the abundance of UNC-52 in late larval stages and increase the frequency of distal tip cell (DTC) migration defects caused by mutations disrupting the UNC-6/netrin guidance system. These unc-52 alleles do not cause circumferential DTC migration defects in an otherwise wild-type genetic background. The effects of unc-52 mutations on DTC migrations are distinct from effects on myofilament organization and can be partially suppressed by mutations in several genes encoding growth factor-like molecules, including EGL-17/FGF, UNC-129/TGF-beta, DBL-1/TGF-beta, and EGL-20/WNT. We propose that UNC-52 serves dual roles in C. elegans larval development in the maintenance of muscle structure and the regulation of growth factor-like signaling pathways.
authors.affiliation: Department of Molecular and Medical Genetics, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: David C
authors.initials: DC
authors.lastname: Merz
authors.forename: Georges
authors.initials: G
authors.lastname: Alves
authors.forename: Takehiro
authors.initials: T
authors.lastname: Kawano
authors.forename: Hong
authors.initials: H
authors.lastname: Zheng
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Culotti
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics; D012734:Disorders of Sex Development; D005260:Female; D017238:Genes, Helminth; D006066:Gonads / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism; D006133:Growth Substances / Q000235:genetics / Q000378:metabolism; D015801:Helminth Proteins / Q000235:genetics* / Q000378:metabolism; D007814:Larva / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins; D009132:Muscles / Q000378:metabolism; D009154:Mutation; D009419:Nerve Tissue Proteins; D000075385:Netrins; D010641:Phenotype; D017027:Protein Tyrosine Phosphatases / Q000235:genetics; D011509:Proteoglycans / Q000235:genetics* / Q000378:metabolism; D054557:Receptor-Like Protein Tyrosine Phosphatases; D011956:Receptors, Cell Surface / Q000235:genetics; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics; D015398:Signal Transduction
chemical_list: D029742:Caenorhabditis elegans Proteins; C112493:EGL-15 protein, C elegans; D006133:Growth Substances; D015801:Helminth Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D000075385:Netrins; D011509:Proteoglycans; D011956:Receptors, Cell Surface; D017468:Receptors, Fibroblast Growth Factor; C078146:UNC-6 protein, C elegans; C082396:unc-52 protein, C elegans; C077588:UNC-5 protein, C elegans; C112492:CLR-1 protein, C elegans; D017027:Protein Tyrosine Phosphatases; D054557:Receptor-Like Protein Tyrosine Phosphatases