an obligatory role of mind bomb-1 in notch signaling of mammalian development每一个角色的思想bomb-1在切口哺乳动物发展的信号.pdfVIP

An Obligatory Role of Mind Bomb-1 in Notch Signaling of Mammalian Development 1. 1. 1. 1 1 2 1 3,4 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 Kong1* 1 Division of Molecular and Life Sciences, Pohang University of Science and Technology, Pohang, Kyungbuk, South Korea, 2 Department of Biology, Chungnam National University, Daejeon, South Korea, 3 Howard Hughes Medical Institute, Department of Physiology, University of California at San Francisco, San Francisco, California, United States of America, 4 Howard Hughes Medical Institute, Department of Biochemistry, University of California at San Francisco, San Francisco, California, United States of America 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 2/ 2 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