PUBLICATION

Genome-wide loss-of-function analysis of deubiquitylating enzymes for zebrafish development

Authors
Tse, W.K., Eisenhaber, B., Ho, S.H., Ng, Q., Eisenhaber, F., and Jiang, Y.J.
ID
ZDB-PUB-100105-30
Date
2009
Source
BMC Genomics   10: 637 (Journal)
Registered Authors
Ho, Steven, Jiang, Yun-Jin, Tse, Ka Fai William
Keywords
none
MeSH Terms
  • Animals
  • Body Patterning
  • Bone Morphogenetic Proteins/genetics
  • Embryo, Nonmammalian
  • Embryonic Development
  • Endopeptidases/genetics*
  • Gene Expression Regulation, Developmental
  • Gene Knockdown Techniques
  • Receptors, Notch/genetics
  • Sequence Analysis, DNA
  • Zebrafish/embryology
  • Zebrafish/genetics*
  • Zebrafish Proteins/genetics*
PubMed
20040115 Full text @ BMC Genomics
Abstract
BACKGROUND: Deconjugation of ubiquitin and/or ubiquitin-like modified protein substrates is essential to modulate protein-protein interactions and, thus, signaling processes in cells. Although deubiquitylating (deubiquitinating) enzymes (DUBs) play a key role in this process, however, their function and regulation remain insufficiently understood. The "loss-of-function" phenotype studies can provide important information to elucidate the gene function, and zebrafish is an excellent model for this goal. RESULTS: From an in silico genome-wide search, we found more than 90 putative DUBs encoded in the zebrafish genome belonging to six different subclasses. Out of them, 85 from five classical subclasses have been tested with morpholino (MO) knockdown experiments and 57 of them were found to be important in early development of zebrafish. These DUB morphants resulted in a complex and pleiotropic phenotype that, regardless of gene target, always affected the notochord. Based on the huC neuronal marker expression, we grouped them into five sets (groups I to V). Group I DUBs (otud7b, uchl3 and bap1) appear to be involved in the Notch signaling pathway based on the neuronal hyperplasia, while group IV DUBs (otud4, usp5, usp15 and usp25) play a critical role in dorsoventral patterning through the BMP pathway. CONCLUSION: We have identified an exhaustive list of genes in the zebrafish genome belonging to the five established classes of DUBs. Additionally, we performed the corresponding MO knockdown experiments in zebrafish as well as functional studies for a subset of the predicted DUB genes. The screen results in this work will stimulate functional follow-up studies of potential DUB genes using the zebrafish model system.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping