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Gene Review

mib1  -  mindbomb E3 ubiquitin protein ligase 1

Danio rerio

Synonyms: E3 ubiquitin-protein ligase mib1, Protein mind bomb, SO:0000704, cg5841, chunp6889, ...
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Disease relevance of mib

  • Furthermore, multi-cilia cell hyperplasia was observed in mind bomb mutants and Mind bomb was shown to interact with Jagged2a and facilitate its internalization [1].

High impact information on mib

  • Delta is directly ubiquitinated by Drosophila and Xenopus Neuralized, and by zebrafish Mind bomb, two unrelated RING-type E3 ubiquitin ligases with common abilities to promote Delta endocytosis and signaling activity [2].
  • Recent findings indicate that, paradoxically, endocytosis of a membrane-spanning ligand may up-regulate receptor activity: the zebrafish E3 ligase Mind bomb promotes the endocytosis of Delta and is required for efficient activation of Notch [3].
  • Furthermore, by functional analysis of three conserved regions of Mind bomb, we show that the N-terminal half is required for Delta association, the ankyrin repeats are important for Delta internalization, and the ring fingers are required for Delta ubiquitination [4].
  • In mind bomb (mib) mutants, in which delta-mediated notch signalling is defective [Dev. Cell 4 (2003) 67], ptf1a is normally expressed [5].
  • We crossed mind bomb (mib) fish with this line to visualize their neurogenic phenotype in live mib(-/-) mutant embryos [6].

Biological context of mib


Anatomical context of mib

  • Hindbrain branchiomotor neurons (BMNs) are reduced in number but not missing in mib mutants [7].
  • Failure of lateral inhibition mediated by Notch signaling is associated with an overproduction of ear hair cells in the zebrafish mind bomb (mib) and deltaA mutants (Development 125 (1998a) 4637; Development 126 (1999) 5669), suggesting a similar role for these genes in limiting the number of hair cells in the zebrafish ear [8].

Regulatory relationships of mib

  • Thus, the three functionally distinct modules of Mind bomb work cooperatively to regulate Notch signaling by associating with, ubiquitinating, and internalizing Delta [4].

Other interactions of mib

  • Cell transplantation studies suggest that mib function is essential in the signaling cell for efficient activation of Notch in neighboring cells [9].
  • Driving wnt1 expression using a heat-shock construct partially rescues metameric patterning in mib mutants [10].


  1. Jagged2a-notch signaling mediates cell fate choice in the zebrafish pronephric duct. Ma, M., Jiang, Y.J. PLoS Genet. (2007) [Pubmed]
  2. The ubiquitin ligase Drosophila Mind bomb promotes Notch signaling by regulating the localization and activity of Serrate and Delta. Lai, E.C., Roegiers, F., Qin, X., Jan, Y.N., Rubin, G.M. Development (2005) [Pubmed]
  3. Notch signaling: endocytosis makes delta signal better. Le Borgne, R., Schweisguth, F. Curr. Biol. (2003) [Pubmed]
  4. Three modules of zebrafish Mind bomb work cooperatively to promote Delta ubiquitination and endocytosis. Chen, W., Casey Corliss, D. Dev. Biol. (2004) [Pubmed]
  5. Evolutionary conserved role of ptf1a in the specification of exocrine pancreatic fates. Zecchin, E., Mavropoulos, A., Devos, N., Filippi, A., Tiso, N., Meyer, D., Peers, B., Bortolussi, M., Argenton, F. Dev. Biol. (2004) [Pubmed]
  6. Analysis of upstream elements in the HuC promoter leads to the establishment of transgenic zebrafish with fluorescent neurons. Park, H.C., Kim, C.H., Bae, Y.K., Yeo, S.Y., Kim, S.H., Hong, S.K., Shin, J., Yoo, K.W., Hibi, M., Hirano, T., Miki, N., Chitnis, A.B., Huh, T.L. Dev. Biol. (2000) [Pubmed]
  7. Neurogenic phenotype of mind bomb mutants leads to severe patterning defects in the zebrafish hindbrain. Bingham, S., Chaudhari, S., Vanderlaan, G., Itoh, M., Chitnis, A., Chandrasekhar, A. Dev. Dyn. (2003) [Pubmed]
  8. Expression of proneural and neurogenic genes in the zebrafish lateral line primordium correlates with selection of hair cell fate in neuromasts. Itoh, M., Chitnis, A.B. Mech. Dev. (2001) [Pubmed]
  9. Mind bomb is a ubiquitin ligase that is essential for efficient activation of Notch signaling by Delta. Itoh, M., Kim, C.H., Palardy, G., Oda, T., Jiang, Y.J., Maust, D., Yeo, S.Y., Lorick, K., Wright, G.J., Ariza-McNaughton, L., Weissman, A.M., Lewis, J., Chandrasekharappa, S.C., Chitnis, A.B. Dev. Cell (2003) [Pubmed]
  10. Rhombomere boundaries are Wnt signaling centers that regulate metameric patterning in the zebrafish hindbrain. Riley, B.B., Chiang, M.Y., Storch, E.M., Heck, R., Buckles, G.R., Lekven, A.C. Dev. Dyn. (2004) [Pubmed]
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