RRC ID 4253
Author Komatsu H, Chao MY, Larkins-Ford J, Corkins ME, Somers GA, Tucey T, Dionne HM, White JQ, Wani K, Boxem M, Hart AC.
Title OSM-11 facilitates LIN-12 Notch signaling during Caenorhabditis elegans vulval development.
Journal PLoS Biol.
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.
Volume 6(8)
Pages e196
Published 2008-8-12
DOI 10.1371/journal.pbio.0060196
PII 08-PLBI-RA-1773
PMID 18700817
PMC PMC2504490
MeSH Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Caenorhabditis elegans Proteins / physiology* Calcium-Binding Proteins / genetics Drosophila Proteins Female Intercellular Signaling Peptides and Proteins / genetics Intracellular Signaling Peptides and Proteins / genetics Intracellular Signaling Peptides and Proteins / physiology* Jagged-1 Protein MAP Kinase Kinase Kinases / genetics MAP Kinase Kinase Kinases / metabolism Membrane Proteins / genetics Membrane Proteins / physiology* Receptors, Notch / physiology* Serrate-Jagged Proteins Signal Transduction Vulva / physiology
IF 8.386
Times Cited 73
WOS Category BIOLOGY BIOCHEMISTRY & MOLECULAR BIOLOGY
Resource
C.elegans tm2256