High-throughput sequencing analyses of XX genital ridges lacking FOXL2 reveal DMRT1 up-regulation before SOX9 expression during the sex-reversal process in goats.
FOXL2 loss of function in goats leads to the early transdifferentiation of ovaries into testes, then to the full sex reversal of XX homozygous mutants. By contrast, Foxl2 loss of function in mice induces an arrest of follicle formation after birth, followed by complete female sterility. In order to understand the molecular role of FOXL2 during ovarian differentiation in the goat species, putative FOXL2 target genes were determined at the earliest stage of gonadal sex-specific differentiation by comparing the mRNA profiles of XX gonads expressing the FOXL2 protein or not. Of these 163 deregulated genes, around two-thirds corresponded to testicular genes that were up-regulated when FOXL2 was absent, and only 19 represented female-associated genes, down-regulated in the absence of FOXL2. FOXL2 should therefore be viewed as an antitestis gene rather than as a female-promoting gene. In particular, the key testis-determining gene DMRT1 was found to be up-regulated ahead of SOX9, thus suggesting in goats that SOX9 primary up-regulation may require DMRT1. Overall, our results equated to FOXL2 being an antitestis gene, allowing us to propose an alternative model for the sex-determination process in goats that differs slightly from that demonstrated in mice.
INRA, UMR 1198, Biologie du Développement et Reproduction, Jouy-en-Josas, France.
Maëva
M
Elzaiat
INRA, UMR 1198, Biologie du Développement et Reproduction, Jouy-en-Josas, France.
Luc
L
Jouneau
INRA, UMR 1198, Biologie du Développement et Reproduction, Jouy-en-Josas, France.
Dominique
D
Thépot
INRA, Sigenae UR875 BIA, Castanet-Tolosan Cedex, France.
Christophe
C
Klopp
INRA, UMR 1198, Biologie du Développement et Reproduction, Jouy-en-Josas, France.
Aurélie
A
Allais-Bonnet
INRA, Sigenae GenPhySE (Génétique, Physiologie et Systèmes d'Elevage), Castanet-Tolosan, France.
Cédric
C
Cabau
INRA, UMR 1198, Biologie du Développement et Reproduction, Jouy-en-Josas, France.
Marjolaine
M
André
INRA, UMR1313 Génétique Animale et Biologie Intégrative, Jouy-en-Josas, France.
Stéphane
S
Chaffaux
INRA, UMR1313 Génétique Animale et Biologie Intégrative, Jouy-en-Josas, France.
Edmond-Paul
EP
Cribiu
INRA, UMR 1198, Biologie du Développement et Reproduction, Jouy-en-Josas, France.
Eric
E
Pailhoux
INRA, UMR 1198, Biologie du Développement et Reproduction, Jouy-en-Josas, France maelle.pannetier@jouy.inra.fr.
Maëlle
M
Pannetier
D058531:46, XX Testicular Disorders of Sex Development / Q000235:genetics* / Q000662:veterinary; D000818:Animals; D030801:Animals, Genetically Modified; D054338:Cell Transdifferentiation; D004622:Embryo, Mammalian; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D005836:Genitalia, Female / Q000196:embryology / Q000378:metabolism*; D006041:Goats / Q000235:genetics / Q000502:physiology*; D059014:High-Throughput Nucleotide Sequencing; D008297:Male; D010053:Ovary / Q000378:metabolism; D055758:SOX9 Transcription Factor / Q000235:genetics*; D019849:Sex Determination Processes / Q000235:genetics; D013737:Testis / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics*; D015854:Up-Regulation
C110547:DMRT1 protein; D051858:Forkhead Transcription Factors; D055758:SOX9 Transcription Factor; D014157:Transcription Factors
DMRT1; FOXL2; RNA sequencing; XX sex reversal; comparative genetics; goat; sex-determination