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


RESULTS
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
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.
Division of Molecular and Life Sciences, Pohang University of Science and Technology, Pohang, Kyungbuk, South Korea.
Bon-Kyoung
BK
Koo
Mi-Jeong
MJ
Yoon
Ki-Jun
KJ
Yoon
Sun-Kyoung
SK
Im
Yoon-Young
YY
Kim
Cheol-Hee
CH
Kim
Pann-Ghill
PG
Suh
Yuh Nung
YN
Jan
Young-Yun
YY
Kong
D000818:Animals; D047108:Embryonic Development / Q000502:physiology*; D005091:Exons; D020868:Gene Silencing; D000072101:Jagged-2 Protein; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000502:physiology*
C490503:Jag2 protein, mouse; D000072101:Jagged-2 Protein; D008565:Membrane Proteins; D051880:Receptors, Notch; C470629:MIB1 protein, mouse; D044767:Ubiquitin-Protein Ligases