Mind bomb 1 is essential for generating functional Notch ligands to activate Notch

Bon‐Kyoung Koo(Pohang University of Science and Technology), Hyoung–Soo Lim(Pohang University of Science and Technology), Ran Song(Pohang University of Science and Technology), Mi-Jeong Yoon(Pohang University of Science and Technology), Ki‐Jun Yoon(Pohang University of Science and Technology), Jin-Sook Moon(Pohang University of Science and Technology), Young-Woong Kim(Pohang University of Science and Technology), Min‐Chul Kwon(Pohang University of Science and Technology), Kyeong-Won Yoo(Chungnam National University), Myung-Phil Kong(Pohang University of Science and Technology), Jinie Lee(Pohang University of Science and Technology), Ajay Chitnis(Eunice Kennedy Shriver National Institute of Child Health and Human Development), Cheol‐Hee Kim(Chungnam National University), Young‐Yun Kong(Pohang University of Science and Technology)
Development
July 7, 2005
10.1242/dev.01922
Cited by 247

Abstract

The Delta-Notch signaling pathway is an evolutionarily conserved intercellular signaling mechanism essential for cell fate specification. Mind bomb 1 (Mib1) has been identified as a ubiquitin ligase that promotes the endocytosis of Delta. We now report that mice lacking Mib1 die prior to embryonic day 11.5, with pan-Notch defects in somitogenesis, neurogenesis, vasculogenesis and cardiogenesis. The Mib1-/- embryos exhibit reduced expression of Notch target genes Hes5, Hey1, Hey2 and Heyl, with the loss of N1icd generation. Interestingly, in the Mib1-/- mutants, Dll1 accumulated in the plasma membrane, while it was localized in the cytoplasm near the nucleus in the wild types, indicating that Mib1 is essential for the endocytosis of Notch ligand. In accordance with the pan-Notch defects in Mib1-/- embryos, Mib1 interacts with and regulates all of the Notch ligands, jagged 1 and jagged 2, as well as Dll1, Dll3 and Dll4. Our results show that Mib1 is an essential regulator, but not a potentiator, for generating functional Notch ligands to activate Notch signaling.

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