PUBLICATION
Mind bomb 1 is essential for generating functional Notch ligands to activate Notch
- Authors
- Koo, B.K., Lim, H.S., Song, R., Yoon, M.J., Yoon, K.J., Moon, J.S., Kim, Y.W., Kwon, M.C., Yoo, K.W., Kong, M.P., Lee, J., Chitnis, A.B., Kim, C.H., and Kong, Y.Y.
- ID
- ZDB-PUB-060627-3
- Date
- 2005
- Source
- Development (Cambridge, England) 132(15): 3459-3470 (Journal)
- Registered Authors
- Chitnis, Ajay, Kim, Cheol-Hee, Yoo, Kyeong-Won
- Keywords
- Notch signaling, Mind bomb, Endocytosis, Notch ligand, Mouse
- MeSH Terms
-
- Animals
- Blood Vessels/embryology
- Embryonic Development/genetics
- Gene Expression Regulation, Developmental
- Heart/embryology
- Ligands
- Membrane Proteins/metabolism*
- Mice
- Mice, Knockout
- Receptors, Cell Surface/metabolism
- Receptors, Notch
- Reverse Transcriptase Polymerase Chain Reaction
- Ubiquitin-Protein Ligases/deficiency
- Ubiquitin-Protein Ligases/genetics*
- PubMed
- 16000382 Full text @ Development
Citation
Koo, B.K., Lim, H.S., Song, R., Yoon, M.J., Yoon, K.J., Moon, J.S., Kim, Y.W., Kwon, M.C., Yoo, K.W., Kong, M.P., Lee, J., Chitnis, A.B., Kim, C.H., and Kong, Y.Y. (2005) Mind bomb 1 is essential for generating functional Notch ligands to activate Notch. Development (Cambridge, England). 132(15):3459-3470.
Abstract
The Delta-Notch signaling pathway is an evolutionarily conserved intercellular signaling mechanism essential for cell fate specification. Mind bomb 1 (Mib1) has been identified as a ubiquitin ligase that promotes the endocytosis of Delta. We now report that mice lacking Mib1 die prior to embryonic day 11.5, with pan-Notch defects in somitogenesis, neurogenesis, vasculogenesis and cardiogenesis. The Mib1-/- embryos exhibit reduced expression of Notch target genes Hes5, Hey1, Hey2 and Heyl, with the loss of N1icd generation. Interestingly, in the Mib1-/- mutants, Dll1 accumulated in the plasma membrane, while it was localized in the cytoplasm near the nucleus in the wild types, indicating that Mib1 is essential for the endocytosis of Notch ligand. In accordance with the pan-Notch defects in Mib1-/- embryos, Mib1 interacts with and regulates all of the Notch ligands, jagged 1 and jagged 2, as well as Dll1, Dll3 and Dll4. Our results show that Mib1 is an essential regulator, but not a potentiator, for generating functional Notch ligands to activate Notch signaling.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping