title: Hyperproliferation of mitotically active germ cells due to defective anti-Müllerian hormone signaling mediates sex reversal in medaka.
abstract: The function of AMH (Anti-Müllerian hormone), a phylogenetically ancient member of the TGFβ family of proteins, in lower vertebrates is largely unknown. Previously, we have shown that the gene encoding the type II anti-Müllerian hormone receptor, amhrII, is responsible for excessive germ cell proliferation and male-to-female sex reversal in the medaka hotei mutant. In this study, functional analyses in cultured cells and of other amhrII mutant alleles indicate that lack of AMH signaling causes the hotei phenotype. BrdU incorporation experiments identified the existence of both quiescent and mitotically active germ cells among the self-renewing, type I population of germ cells in the developing gonad. AMH signaling acts in supporting cells to promote the proliferation of mitotically active germ cells but does not trigger quiescent germ cells to proliferate in the developing gonad. Furthermore, we show that the male-to-female sex reversal phenotype in hotei mutants is not a direct consequence of AMH signaling in supporting cells, but is instead mediated by germ cells. Our data demonstrate that interfollicular AMH signaling regulates proliferation at a specific stage of germ cell development, and that this regulation is crucial for the proper manifestation of gonadal sex directed by sex determination genes.
authors.affiliation: Laboratory of Molecular Genetics for Reproduction, National Institute for Basic Biology, Higashiyama 5-1, Okazaki, Aichi 444-8787, Japan.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Nakamura
authors.forename: Ikuko
authors.initials: I
authors.lastname: Watakabe
authors.forename: Toshiya
authors.initials: T
authors.lastname: Nishimura
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Picard
authors.forename: Atsushi
authors.initials: A
authors.lastname: Toyoda
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Taniguchi
authors.forename: Nathalie
authors.initials: N
authors.lastname: di Clemente
authors.forename: Minoru
authors.initials: M
authors.lastname: Tanaka
mesh_terms: D000818:Animals; D054304:Anti-Mullerian Hormone / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D005854:Germ Cells / Q000166:cytology* / Q000502:physiology; D008297:Male; D008938:Mitosis; D009154:Mutation; D009990:Oryzias / Q000254:growth & development* / Q000378:metabolism; D018000:Receptors, Peptide / Q000235:genetics / Q000378:metabolism*; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D012733:Sex Differentiation; D015398:Signal Transduction
chemical_list: D018000:Receptors, Peptide; D018125:Receptors, Transforming Growth Factor beta; C084621:anti-Mullerian hormone receptor; D054304:Anti-Mullerian Hormone