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Developmental Biology 394 (2014) 242–252

Contents lists available at ScienceDirect

Developmental Biology journal homepage: www.elsevier.com/locate/developmentalbiology

Marker genes identify three somatic cell types in the fetal mouse ovary
Raphael H. Rastetter a,1, Pascal Bernard a,1, James S. Palmer b, Anne-Amandine Chassot c,d,
Huijun Chen b, Patrick S. Western e, Robert G. Ramsay f,g, Marie-Christine Chaboissier c,d,
Dagmar Wilhelm a,n a Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC 3800, Australia
Division of Molecular Genetics and Development, Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4075, Australia c University of Nice-Sophia Antipolis, UFR Sciences, Nice,
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Together, these three marker genes label distinct ovarian somatic cell types. Using lineage tracing in mice, we show that Lgr5-positive cells give rise to adult cortical granulosa cells, which form the follicles of the definitive reserve. Moreover, LGR5 is required for correct timing of germ cell differentiation as evidenced by a delay of entry into meiosis in Lgr5 loss-of-function mutants, demonstrating a key role for LGR5 in the differentiation of pre-granulosa cells, which ensure the differentiation of oogonia, the formation of the definitive follicle reserve, and long-term female fertility.
& 2014 Elsevier Inc. All rights reserved.

Keywords:
Foxl2
Lgr5
Nr2f2
Rspo1
Wnt4
Ovary

Introduction
Ovaries develop from a bipotential anlage, the genital ridges, which arise as paired structures at the ventro-medial surface of the mesonephros at around 10 days post coitum (dpc) in mice.
Approximately half a day later, at 10.5 dpc, the male-determining gene Sry on the Y chromosome is up-regulated in XY genital ridges and drives differentiation into a testis. If Sry is not present, e.g. in an XX individual, or its expression or function is misregulated, the genital ridge will develop into an ovary (Warr and Greenfield,
2012; Wilhelm et al., 2013). The differentiation of an ovary is actively driven by a number of genes, including Wnt4 (winglessrelated MMTV integration site 4)

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