RGD Reference Report - The divergent DSL ligand Dll3 does not activate Notch signaling but cell autonomously attenuates signaling induced by other DSL ligands. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

The divergent DSL ligand Dll3 does not activate Notch signaling but cell autonomously attenuates signaling induced by other DSL ligands.

Authors: Ladi, E  Nichols, JT  Ge, W  Miyamoto, A  Yao, C  Yang, LT  Boulter, J  Sun, YE  Kintner, C  Weinmaster, G 
Citation: Ladi E, etal., J Cell Biol. 2005 Sep 12;170(6):983-92. Epub 2005 Sep 6.
RGD ID: 1599776
Pubmed: PMID:16144902   (View Abstract at PubMed)
PMCID: PMC2171428   (View Article at PubMed Central)
DOI: DOI:10.1083/jcb.200503113   (Journal Full-text)

Mutations in the DSL (Delta, Serrate, Lag2) Notch (N) ligand Delta-like (Dll) 3 cause skeletal abnormalities in spondylocostal dysostosis, which is consistent with a critical role for N signaling during somitogenesis. Understanding how Dll3 functions is complicated by reports that DSL ligands both activate and inhibit N signaling. In contrast to other DSL ligands, we show that Dll3 does not activate N signaling in multiple assays. Consistent with these findings, Dll3 does not bind to cells expressing any of the four N receptors, and N1 does not bind Dll3-expressing cells. However, in a cell-autonomous manner, Dll3 suppressed N signaling, as was found for other DSL ligands. Therefore, Dll3 functions not as an activator as previously reported but rather as a dedicated inhibitor of N signaling. As an N antagonist, Dll3 promoted Xenopus laevis neurogenesis and inhibited glial differentiation of mouse neural progenitors. Finally, together with the modulator lunatic fringe, Dll3 altered N signaling levels that were induced by other DSL ligands.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Notch binding  IPINOTCH1 (Homo sapiens)1599776 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Dll3  (delta like canonical Notch ligand 3)


Additional Information