title: Mutation of zebrafish caf-1b results in S phase arrest, defective differentiation, and p53-mediated apoptosis during organogenesis.
abstract: The cell cycle of multicellular organisms must be tightly coordinated with organogenesis and differentiation. Experiments done in vitro have identified chromatin assembly factor 1 (CAF-1) as a protein complex promoting chromatin assembly during DNA replication, but the in vivo role of CAF-1 in multicellular animals is still poorly understood. Here we describe the characterization of a zebrafish mutant disrupting CAF-1b activity, and show that it leads to defective cell cycle progression and differentiation in several organs, including the retina, optic tectum, pectoral fins, and head skeleton. Retinal precursor cells mutant for caf-1b arrest in S phase and undergo p53-mediated apoptosis. While p53 deficiency is able to rescue apoptosis in caf-1b mutants, it fails to rescue differentiation, indicating that CAF-1 activity is essential for differentiation in these organs. In addition, we also show that regulation of caf-1b expression in the retina depends on a group of genes that regulate the switch from proliferation to differentiation.
authors.affiliation: European Molecular Biology Laboratory, Heidelberg, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Fischer
authors.forename: Sergey
authors.initials: S
authors.lastname: Prykhozhij
authors.forename: Marlene J
authors.initials: MJ
authors.lastname: Rau
authors.forename: Carl J
authors.initials: CJ
authors.lastname: Neumann
mesh_terms: D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D056504:Chromatin Assembly Factor-1; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D009154:Mutation; D038081:Organogenesis; D012160:Retina / Q000166:cytology / Q000196:embryology; D016196:S Phase; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D015027:Zebrafish; D029961:Zebrafish Proteins
chemical_list: D056504:Chromatin Assembly Factor-1; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D016159:Tumor Suppressor Protein p53; D029961:Zebrafish Proteins