PUBLICATION

Mutation in utp15 Disrupts Vascular Patterning in a p53-Dependent Manner in Zebrafish Embryos

Authors
Mouillesseaux, K., and Chen, J.N.
ID
ZDB-PUB-111011-36
Date
2011
Source
PLoS One   6(9): e25013 (Journal)
Registered Authors
Chen, Jau-Nian
Keywords
none
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Apoptosis
  • Blood Vessels/embryology*
  • Blood Vessels/metabolism
  • Cloning, Molecular
  • Embryo, Nonmammalian/cytology
  • Embryo, Nonmammalian/metabolism*
  • Embryonic Development
  • Gene Expression Regulation, Developmental
  • In Situ Hybridization
  • Mutation/genetics*
  • Neovascularization, Physiologic*
  • Phenotype
  • RNA, Messenger/genetics
  • Real-Time Polymerase Chain Reaction
  • Signal Transduction
  • Tumor Suppressor Protein p53/genetics
  • Tumor Suppressor Protein p53/metabolism*
  • Zebrafish/embryology
  • Zebrafish/genetics*
  • Zebrafish/metabolism
  • Zebrafish Proteins/physiology*
PubMed
21949834 Full text @ PLoS One
Abstract

Background

Angiogenesis is the process by which the highly branched and functional vasculature arises from the major vessels, providing developing tissues with nutrients, oxygen, and removing metabolic waste. During embryogenesis, vascular patterning is dependent on a tightly regulated balance between pro- and anti-angiogenic signals, and failure of angiogenesis leads to embryonic lethality. Using the zebrafish as a model organism, we sought to identify genes that influence normal vascular patterning.

Methodology and Principal Findings

In a forward genetic screen, we identified mutant LA1908, which manifests massive apoptosis during early embryogenesis, abnormal expression of several markers of arterial-venous specification, delayed angiogenic sprouting of the intersegmental vessels (ISV), and malformation of the caudal vein plexus (CVP), indicating a critical role for LA1908 in cell survival and angiogenesis. Genetic mapping and sequencing identified a G to A transition in the splice site preceding exon 11 of utp15 in LA1908 mutant embryos. Overexpression of wild type utp15 mRNA suppresses all observed mutant phenotypes, demonstrating a causative relationship between utp15 and LA1908. Furthermore, we found that injecting morpholino oligonucleotides inhibiting p53 translation prevents cell death and rescues the vascular abnormalities, indicating that p53 is downstream of Utp15 deficiency in mediating the LA1908 phenotypes.

Conclusions and Significance

Taken together, our data demonstrate an early embryonic effect of Utp15 deficiency on cell survival and the normal patterning of the vasculature and highlight an anti-angiogenic role of p53 in developing embryos.

Genes / Markers
Figures
Figure Gallery
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Errata and Notes