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

• Published in: PloS one Vol. 2; no. 11; p. e1221
• Main Authors: Koo, Bon-Kyoung, Yoon, Mi-Jeong, Yoon, Ki-Jun, Im, Sun-Kyoung, Kim, Yoon-Young, Kim, Cheol-Hee, Suh, Pann-Ghill, Jan, Yuh Nung, Kong, Young-Yun
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 28-11-2007; Public Library of Science (PLoS)
• Subjects: Animal genetics; Animal tissues; Animals; Antigens; Apoptosis; Brain; Caenorhabditis elegans; Cell fate; Cerebellum; Conditional mutant; Deactivation; Developmental Biology/Developmental Molecular Mechanisms; Developmental Biology/Molecular Development; Drosophila; Embryonic Development - physiology; Endocytosis; Evolutionary Biology/Developmental Molecular Mechanisms; Exons; Gene Silencing; Genetics; Genetics and Genomics/Animal Genetics; Genetics and Genomics/Gene Function; Inactivation; Insects; Jagged-2 Protein; Jagged1 protein; Life sciences; Ligands; Ligases; Mammals; Membrane Proteins - genetics; Mice; Mice, Knockout; Mutants; Mutation; Notch protein; Phenotype; Polymerase Chain Reaction; Proteins; Receptors, Notch - metabolism; Signal transduction; Signal Transduction - physiology; Signaling; Skin; Specifications; Ubiquitin; Ubiquitin-protein ligase; Ubiquitin-Protein Ligases - genetics; Ubiquitin-Protein Ligases - physiology; United States > US; San Francisco California; California
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0001221

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.
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.
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.