Maternal topoisomerase II alpha, not topoisomerase II beta, enables embryonic development of zebrafish top2a-/- mutants. BMC Dev Biol 2011 Nov 23;11:71
Date
11/25/2011Pubmed ID
22111588Pubmed Central ID
PMC3287258DOI
10.1186/1471-213X-11-71Scopus ID
2-s2.0-81555237352 (requires institutional sign-in at Scopus site) 17 CitationsAbstract
BACKGROUND: Genetic alterations in human topoisomerase II alpha (TOP2A) are linked to cancer susceptibility. TOP2A decatenates chromosomes and thus is necessary for multiple aspects of cell division including DNA replication, chromosome condensation and segregation. Topoisomerase II alpha is also required for embryonic development in mammals, as mouse Top2a knockouts result in embryonic lethality as early as the 4-8 cell stage. The purpose of this study was to determine whether the extended developmental capability of zebrafish top2a mutants arises from maternal expression of top2a or compensation from its top2b paralogue.
RESULTS: Here, we describe bloody minded (blm), a novel mutant of zebrafish top2a. In contrast to mouse Top2a nulls, zebrafish top2a mutants survive to larval stages (4-5 day post fertilization). Developmental analyses demonstrate abundant expression of maternal top2a but not top2b. Inhibition or poisoning of maternal topoisomerase II delays embryonic development by extending the cell cycle M-phase. Zygotic top2a and top2b are co-expressed in the zebrafish CNS, but endogenous or ectopic top2b RNA appear unable to prevent the blm phenotype.
CONCLUSIONS: We conclude that maternal top2a enables zebrafish development before the mid-zygotic transition (MZT) and that zebrafish top2a and top2b are not functionally redundant during development after activation of the zygotic genome.
Author List
Sapetto-Rebow B, McLoughlin SC, O'Shea LC, O'Leary O, Willer JR, Alvarez Y, Collery R, O'Sullivan J, Van Eeden F, Hensey C, Kennedy BNAuthor
Ross F. Collery PhD Associate Professor in the Ophthalmology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAntigens, Neoplasm
Base Sequence
Cell Cycle
Cell Extracts
DNA Topoisomerases, Type II
DNA-Binding Proteins
Diketopiperazines
Embryonic Development
Female
Gene Expression
Gene Knockout Techniques
Genes, Recessive
Isoenzymes
Male
Phenotype
Phylogeny
Piperazines
Point Mutation
Poly-ADP-Ribose Binding Proteins
Sequence Analysis, DNA
Viviparity, Nonmammalian
Xenopus
Zebrafish
Zebrafish Proteins
Zygote
