title: OSM-11 facilitates LIN-12 Notch signaling during Caenorhabditis elegans vulval development.
abstract: Notch signaling is critical for cell fate decisions during development. Caenorhabditis elegans and vertebrate Notch ligands are more diverse than classical Drosophila Notch ligands, suggesting possible functional complexities. Here, we describe a developmental role in Notch signaling for OSM-11, which has been previously implicated in defecation and osmotic resistance in C. elegans. We find that complete loss of OSM-11 causes defects in vulval precursor cell (VPC) fate specification during vulval development consistent with decreased Notch signaling. OSM-11 is a secreted, diffusible protein that, like previously described C. elegans Delta, Serrate, and LAG-2 (DSL) ligands, can interact with the lineage defective-12 (LIN-12) Notch receptor extracellular domain. Additionally, OSM-11 and similar C. elegans proteins share a common motif with Notch ligands from other species in a sequence defined here as the Delta and OSM-11 (DOS) motif. osm-11 loss-of-function defects in vulval development are exacerbated by loss of other DOS-motif genes or by loss of the Notch ligand DSL-1, suggesting that DOS-motif and DSL proteins act together to activate Notch signaling in vivo. The mammalian DOS-motif protein Deltalike1 (DLK1) can substitute for OSM-11 in C. elegans development, suggesting that DOS-motif function is conserved across species. We hypothesize that C. elegans OSM-11 and homologous proteins act as coactivators for Notch receptors, allowing precise regulation of Notch receptor signaling in developmental programs in both vertebrates and invertebrates.
authors.affiliation: Massachusetts General Hospital, Center for Cancer Research, Charlestown, Massachusetts, United States of America,
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Komatsu
authors.forename: Michael Y
authors.initials: MY
authors.lastname: Chao
authors.forename: Jonah
authors.initials: J
authors.lastname: Larkins-Ford
authors.forename: Mark E
authors.initials: ME
authors.lastname: Corkins
authors.forename: Gerard A
authors.initials: GA
authors.lastname: Somers
authors.forename: Tim
authors.initials: T
authors.lastname: Tucey
authors.forename: Heather M
authors.initials: HM
authors.lastname: Dionne
authors.forename: Jamie Q
authors.initials: JQ
authors.lastname: White
authors.forename: Khursheed
authors.initials: K
authors.lastname: Wani
authors.forename: Mike
authors.initials: M
authors.lastname: Boxem
authors.forename: Anne C
authors.initials: AC
authors.lastname: Hart
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002135:Calcium-Binding Proteins / Q000235:genetics; D029721:Drosophila Proteins; D005260:Female; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology*; D000072100:Jagged-1 Protein; D020930:MAP Kinase Kinase Kinases / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051880:Receptors, Notch / Q000502:physiology*; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction; D014844:Vulva / Q000502:physiology
chemical_list: D029742:Caenorhabditis elegans Proteins; D002135:Calcium-Binding Proteins; D029721:Drosophila Proteins; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; C082460:Lin-12 protein, C elegans; D008565:Membrane Proteins; C532484:OSM-11 protein, C elegans; D051880:Receptors, Notch; C000606278:Ser protein, Drosophila; D000072099:Serrate-Jagged Proteins; C086488:lag-2 protein, C elegans; C498050:DLK-1 protein, C elegans; D020930:MAP Kinase Kinase Kinases