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Publication : An obligatory role of mind bomb-1 in notch signaling of mammalian development.

First Author  Koo BK Year  2007
Journal  PLoS One Volume  2
Issue  11 Pages  e1221
PubMed ID  18043734 Mgi Jnum  J:130369
Mgi Id  MGI:3771527 Doi  10.1371/journal.pone.0001221
Citation  Koo BK, et al. (2007) An obligatory role of mind bomb-1 in notch signaling of Mammalian development. PLoS One 2(11):e1221
abstractText  BACKGROUND: The Notch signaling pathway is an evolutionarily conserved intercellular signaling module essential for cell fate specification that requires endocytosis of Notch ligands. Structurally distinct E3 ubiquitin ligases, Neuralized (Neur) and Mind bomb (Mib), cooperatively regulate the endocytosis of Notch ligands in Drosophila. However, the respective roles of the mammalian E3 ubiquitin ligases, Neur1, Neur2, Mib1, and Mib2, in mammalian development are poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: Through extensive use of mammalian genetics, here we show that Neur1 and Neur2 double mutants and Mib2(-/-) mice were viable and grossly normal. In contrast, conditional inactivation of Mib1 in various tissues revealed the representative Notch phenotypes: defects of arterial specification as deltalike4 mutants, abnormal cerebellum and skin development as jagged1 conditional mutants, and syndactylism as jagged2 mutants. CONCLUSIONS/SIGNIFICANCE: Our data provide the first evidence that Mib1 is essential for Jagged as well as Deltalike ligand-mediated Notch signaling in mammalian development, while Neur1, Neur2, and Mib2 are dispensable.
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