Citation:
Development. 2008 Feb 20; [Epub ahead of print]
Abstract:
Apoptosis is often observed in developing tissues. However, it remains unclear how the apoptotic pathway is regulated during development. To clarify this issue, we isolated zebrafish mutants that show extensive apoptosis of retinal cells during their development. pinball eye (piy) is one such mutant, in which retinal stem cells proliferate normally but almost all retinal neurons undergo apoptosis during differentiation. We found that a missense mutation occurred in the small subunit of DNA primase (Prim1) in the piy mutant. DNA primase is essential for DNA replication; however, this mutation does not affect cell proliferation but rather induces neuronal apoptosis. RNA synthesis catalyzed by Prim1 is important for the activation of the DNA damage response, which may activate Ataxia telangiectasia mutated (ATM), Checkpoint kinase 2 (Chk2) and the tumor suppressor p53. We found that the apoptosis induced by the prim1 mutation depends on the ATM-Chk2-p53 apoptotic pathway. These data suggest that the surveillance system of genome integrity strongly influences the cell fate decision between differentiation and apoptosis during retinal neurogenesis in zebrafish.
Organism or Cell Type:
zebrafish