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


ABSTRACT:

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.

SUBMITTER: Koo BK 

PROVIDER: S-EPMC2082076 | biostudies-literature | 2007 Nov

REPOSITORIES: biostudies-literature

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Publications

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

Koo Bon-Kyoung BK   Yoon Mi-Jeong MJ   Yoon Ki-Jun KJ   Im Sun-Kyoung SK   Kim Yoon-Young YY   Kim Cheol-Hee CH   Suh Pann-Ghill PG   Jan Yuh Nung YN   Kong Young-Yun YY  

PloS one 20071128 11


<h4>Background</h4>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.<h4>Metho  ...[more]

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