Mind bomb is a ubiquitin ligase that is essential for efficient activation of Notch signaling by Delta. Developmental Cell

Motoyuki Itoh, Cheol-Hee Kim, Gregory Palardy, Takaya Oda, Yun-Jin Jiang, Donovan Maust, Sang-Yeob Yeo, Kevin Lorick, Gavin J Wright, Linda Ariza-McNaughton, Allan M Weissman, Julian Lewis, Settara C Chandrasekharappa, Ajay B Chitnis

Research output: Contribution to journalArticlepeer-review


Lateral inhibition, mediated by Notch signaling, leads to the selection of cells that are permitted to become neurons within domains defined by proneural gene expression. Reduced lateral inhibition in zebrafish mib mutant embryos permits too many neural progenitors to differentiate as neurons. Positional cloning of mib revealed that it is a gene in the Notch pathway that encodes a RING ubiquitin ligase. Mib interacts with the intracellular domain of Delta to promote its ubiquitylation and internalization. Cell transplantation studies suggest that mib function is essential in the signaling cell for efficient activation of Notch in neighboring cells. These observations support a model for Notch activation where the Delta-Notch interaction is followed by endocytosis of Delta and transendocytosis of the Notch extracellular domain by the signaling cell. This facilitates intramembranous cleavage of the remaining Notch receptor, release of the Notch intracellular fragment, and activation of target genes in neighboring cells.
Original languageEnglish
Pages (from-to)67-82
Number of pages16
JournalDevelopmental Cell
Issue number1
Publication statusPublished - 2003

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