An Obligatory Role of Mind Bomb-1 in Notch Signaling of Mammalian Development

• DOI: 10.1371/journal.pone.0001221
• Publication Date: 2007-11-27T22:38:09Z
• Authors: Bon-Kyoung Koo; Mi-Jeong Yoon; Ki-Jun Yoon; Sun-Kyoung Im; Yoon-Young Kim; Cheol-Hee Kim; Pann-Ghill Suh; Yuh Nung Jan; Young-Yun Kong
• Keywords: Notch proteins; Hes3 signaling axis; Cell fate determination

The Notch signaling pathway is an evolutionarily conserved intercellular module essential for cell fate specification that requires endocytosis of ligands. Structurally distinct E3 ubiquitin ligases, Neuralized (Neur) and Mind bomb (Mib), cooperatively regulate the ligands in Drosophila. However, respective roles mammalian Neur1, Neur2, Mib1, Mib2, development are poorly understood.Through extensive use genetics, here we show Neur1 Neur2 double mutants Mib2(-/-) mice were viable grossly normal. In contrast, conditional inactivation Mib1 various tissues revealed representative phenotypes: defects arterial as deltalike4 mutants, abnormal cerebellum skin jagged1 syndactylism jagged2 mutants.Our data provide first evidence Jagged well Deltalike ligand-mediated development, while Mib2 dispensable.