Abstract |
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.
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Authors | Ena Ladi, James T Nichols, Weihong Ge, Alison Miyamoto, Christine Yao, Liang-Tung Yang, Jim Boulter, Yi E Sun, Chris Kintner, Gerry Weinmaster |
Journal | The Journal of cell biology
(J Cell Biol)
Vol. 170
Issue 6
Pg. 983-92
(Sep 12 2005)
ISSN: 0021-9525 [Print] United States |
PMID | 16144902
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Intracellular Signaling Peptides and Proteins
- Ligands
- Membrane Proteins
- Tubulin
- delta protein
- Luciferases
- Glycosyltransferases
- Lfng protein, mouse
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Topics |
- Animals
- Biotinylation
- Cell Line
- Coculture Techniques
- Embryonic Development
- Glycosyltransferases
(metabolism)
- Intracellular Signaling Peptides and Proteins
- L Cells
- Ligands
- Luciferases
(metabolism)
- Membrane Proteins
(genetics)
- Mice
- Mutation
- NIH 3T3 Cells
- Neurons
(chemistry, metabolism)
- Rats
- Signal Transduction
- Tubulin
(metabolism)
- Xenopus laevis
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