ZFIN ID: ZDB-PUB-070303-40
The characterization of zebrafish antimorphic mib alleles reveals that Mib and Mind bomb-2 (Mib2) function redundantly
Zhang, C., Li, Q., Lim, C.H., Qiu, X., and Jiang, Y.J.
Date: 2007
Source: Developmental Biology   305(1): 14-27 (Journal)
Registered Authors: Jiang, Yun-Jin, Lim, Chiaw Hwee, Qiu, Xuehui, Zhang, Chengjin
Keywords: Mib homologs, mib alleles, Delta, Notch, E3 ligase, Endocytosis
MeSH Terms:
  • Alleles*
  • Animals
  • Cloning, Molecular
  • Embryo, Nonmammalian/metabolism
  • Gene Expression Regulation/physiology
  • Immunohistochemistry
  • In Situ Hybridization
  • Mutation/genetics
  • Oligonucleotides, Antisense
  • Receptors, Notch/metabolism
  • Signal Transduction/genetics
  • Ubiquitin-Protein Ligases/genetics*
  • Ubiquitin-Protein Ligases/metabolism
  • Zebrafish/genetics*
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
PubMed: 17331493 Full text @ Dev. Biol.
Both mind bomb (mib) and mind bomb-2 (mib2) encode RING E3 ubiquitin ligases that promote Delta ubiquitylation and endocytosis in Notch activation. Detailed morphological and molecular examinations revealed that zebrafish mib(ta52b) (missense mutation in the C-terminal RING Finger (RF), M1013R) and mib(m132) (nonsense mutation resulting in a truncated protein that loses all three RFs, C785stop) are strong and weak antimorphic alleles, respectively, compared to the null allele, mib(tfi91) (nonsense mutation resulting in a truncated protein of only 60 amino acids, Y60stop). Zebrafish mib2 ortholog was identified in this study. Zebrafish Mib and Mib2 are colocalized in transfected cells and function redundantly in regulating Notch signaling in embryos. Mib(ta52b) and Mib(m132) have a dosage-dependent dominant-negative effect, at least, on Mib2, which is a molecular basis for the antimorphic phenotypes. It was also shown that Notch signaling negatively regulates mib expression in a Su(H)-dependent manner, forming a negative feedback loop in modulating Notch activation.