Please use this identifier to cite or link to this item:
Title: Sex Reversal in Zebrafish fancl Mutants is Caused by Tp53-Mediated Germ Cell Apoptosis
Author: Rodríguez Marí, Adriana
Cañestro García, Cristian
BreMiller, R. A.
Nguyen-Johnson, A.
Asakawa, K.
Kawakami, K.
Postlethwait, J. H.
Keywords: Peix zebra
Fisiologia animal
Determinació del sexe
Genètica molecular
Zebra danio
Animal physiology
Sex determination
Molecular genetics
Issue Date: Jul-2010
Publisher: Public Library of Science (PLoS)
Abstract: The molecular genetic mechanisms of sex determination are not known for most vertebrates, including zebrafish. We identified a mutation in the zebrafish fancl gene that causes homozygous mutants to develop as fertile males due to female-to-male sex reversal. Fancl is a member of the Fanconi Anemia/BRCA DNA repair pathway. Experiments showed that zebrafish fancl was expressed in developing germ cells in bipotential gonads at the critical time of sexual fate determination. Caspase-3 immunoassays revealed increased germ cell apoptosis in fancl mutants that compromised oocyte survival. In the absence of oocytes surviving through meiosis, somatic cells of mutant gonads did not maintain expression of the ovary gene cyp19a1a and did not down-regulate expression of the early testis gene amh; consequently, gonads masculinized and became testes. Remarkably, results showed that the introduction of a tp53 (p53) mutation into fancl mutants rescued the sex-reversal phenotype by reducing germ cell apoptosis and, thus, allowed fancl mutants to become fertile females. Our results show that Fancl function is not essential for spermatogonia and oogonia to become sperm or mature oocytes, but instead suggest that Fancl function is involved in the survival of developing oocytes through meiosis. This work reveals that Tp53-mediated germ cell apoptosis induces sex reversal after the mutation of a DNA-repair pathway gene by compromising the survival of oocytes and suggests the existence of an oocyte-derived signal that biases gonad fate towards the female developmental pathway and thereby controls zebrafish sex determination.
Note: Reproducció del document publicat a:
It is part of: PLoS Genetics, 2010, vol. 6, num. 7, p. e1001034
Related resource:
ISSN: 1553-7390
Appears in Collections:Articles publicats en revistes (Genètica, Microbiologia i Estadística)

Files in This Item:
File Description SizeFormat 
583815.pdf6.48 MBAdobe PDFView/Open

This item is licensed under a Creative Commons License Creative Commons