Disruption of mitotic arrest precedes precocious differentiation and transdifferentiation of pregranulosa cells in the perinatal Wnt4 mutant ovary.

Journal Article (Journal Article)

Mammalian sex determination is controlled by antagonistic pathways that are initially co-expressed in the bipotential gonad and subsequently become male- or female-specific. In XY gonads, testis development is initiated by upregulation of Sox9 by SRY in pre-Sertoli cells. Disruption of either gene leads to complete male-to-female sex reversal. Ovarian development is dependent on canonical Wnt signaling through Wnt4, Rspo1 and β-catenin. However, only a partial female-to-male sex reversal results from disruption of these ovary-promoting genes. In Wnt4 and Rspo1 mutants, there is evidence of pregranulosa cell-to-Sertoli cell transdifferentiation near birth, following a severe decline in germ cells. It is currently unclear why primary sex reversal does not occur at the sex-determining stage, but instead occurs near birth in these mutants. Here we show that Wnt4-null and Rspo1-null pregranulosa cells transition through a differentiated granulosa cell state prior to transdifferentiating towards a Sertoli cell fate. This transition is preceded by a wave of germ cell death that is closely associated with the disruption of pregranulosa cell quiescence. Our results suggest that maintenance of mitotic arrest in pregranulosa cells may preclude upregulation of Sox9 in cases where female sex-determining genes are disrupted. This may explain the lack of complete sex reversal in such mutants at the sex-determining stage.

Full Text

Duke Authors

Cited Authors

  • Maatouk, DM; Mork, L; Chassot, A-A; Chaboissier, M-C; Capel, B

Published Date

  • November 15, 2013

Published In

Volume / Issue

  • 383 / 2

Start / End Page

  • 295 - 306

PubMed ID

  • 24036309

Pubmed Central ID

  • PMC4066978

Electronic International Standard Serial Number (EISSN)

  • 1095-564X

Digital Object Identifier (DOI)

  • 10.1016/j.ydbio.2013.08.026


  • eng

Conference Location

  • United States