ZFIN ID: ZDB-PUB-050818-6
p53 deficiency rescues apoptosis and differentiation of multiple cell types in zebrafish flathead mutants deficient for zygotic DNA polymerase delta1
Plaster, N., Sonntag, C., Busse, C.E., and Hammerschmidt, M.
Date: 2006
Source: Cell death and differentiation   13(2): 223-235 (Journal)
Registered Authors: Hammerschmidt, Matthias, Plaster, Nikki, Sonntag, Carmen
Keywords: DNA polymerase delta1, p53, flathead, zebrafish, replication, apoptosis, S-phase checkpoint
MeSH Terms:
  • Amino Acid Sequence
  • Animals
  • Apoptosis*
  • Brain/cytology
  • Brain/embryology
  • Cell Differentiation*
  • Cell Proliferation
  • DNA Polymerase III/deficiency
  • DNA Polymerase III/genetics
  • DNA Polymerase III/metabolism*
  • DNA Replication
  • Eye/cytology
  • Eye/embryology
  • Female
  • Gene Expression Regulation, Developmental
  • Male
  • Molecular Sequence Data
  • Mutation*
  • Phenotype
  • Reverse Transcriptase Polymerase Chain Reaction
  • S Phase
  • Skull/cytology
  • Skull/embryology
  • Tumor Suppressor Protein p53/deficiency
  • Tumor Suppressor Protein p53/genetics
  • Tumor Suppressor Protein p53/physiology*
  • Up-Regulation/genetics
  • Up-Regulation/physiology
  • Zebrafish/embryology
  • Zebrafish/genetics*
  • Zebrafish/physiology
  • Zygote/cytology
  • Zygote/enzymology
  • Zygote/physiology
PubMed: 16096653 Full text @ Cell Death Differ.
Cell culture work has identified the tumor suppressor p53 as a component of the S-phase checkpoint control system, while in vivo studies of this role of p53 in whole-vertebrate systems were limited. Here, we describe zebrafish mutants in the DNA polymerase delta catalytic subunit 1, based on the positional cloning of the flathead (fla) gene. fla mutants display specific defects in late proliferative zones, such as eyes, brain and cartilaginous elements of the visceral head skeleton, where cells display compromised DNA replication, followed by apoptosis, and partial or complete loss of affected tissues. Antisense-mediated knockdown of p53 in fla mutants leads to a striking rescue of all phenotypic traits, including completion of replication, survival of cells, and normal differentiation and tissue formation. This indicates that under replication-compromised conditions, the p53 branch of the S-phase checkpoint is responsible for eliminating stalled cells that, given more time, would have otherwise finished their normal developmental program.