title: Marker genes identify three somatic cell types in the fetal mouse ovary.
abstract: The two main functions of the ovary are the production of oocytes, which allows the continuation of the species, and secretion of female sex hormones, which control many aspects of female development and physiology. Normal development of the ovaries during embryogenesis is critical for their function and the health of the individual in later life. Although the adult ovary has been investigated in great detail, we are only starting to understand the cellular and molecular biology of early ovarian development. Here we show that the adult stem cell marker Lgr5 is expressed in the cortical region of the fetal ovary and this expression is mutually exclusive to FOXL2. Strikingly, a third somatic cell population can be identified, marked by the expression of NR2F2, which is expressed in LGR5- and FOXL2 double-negative ovarian somatic cells. 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.
authors.affiliation: Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC 3800, Australia.
authors.forename: Raphael H
authors.initials: RH
authors.lastname: Rastetter
authors.affiliation: Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC 3800, Australia.
authors.forename: Pascal
authors.initials: P
authors.lastname: Bernard
authors.affiliation: Division of Molecular Genetics and Development, Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4075, Australia.
authors.forename: James S
authors.initials: JS
authors.lastname: Palmer
authors.affiliation: University of Nice-Sophia Antipolis, UFR Sciences, Nice, France; INSERM U1091, CNRS UMR7277, IBV, Nice, France.
authors.forename: Anne-Amandine
authors.initials: AA
authors.lastname: Chassot
authors.affiliation: Division of Molecular Genetics and Development, Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4075, Australia.
authors.forename: Huijun
authors.initials: H
authors.lastname: Chen
authors.affiliation: MIMR-PHI Institute of Medical Research, Clayton, VIC 3800, Australia.
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Western
authors.affiliation: Sir Peter MacCallum, Department of Oncology and the Pathology Department, The University of Melbourne, Parkville, VIC, Australia; Department of Pathology, The University of Melbourne, Parkville, VIC, Australia.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Ramsay
authors.affiliation: University of Nice-Sophia Antipolis, UFR Sciences, Nice, France; INSERM U1091, CNRS UMR7277, IBV, Nice, France.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Chaboissier
authors.affiliation: Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC 3800, Australia. Electronic address: dagmar.wilhelm@monash.edu.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Wilhelm
mesh_terms: D000818:Animals; D051837:COUP Transcription Factor II / Q000378:metabolism; D019070:Cell Lineage / Q000502:physiology; D005260:Female; D005333:Fetus / Q000166:cytology*; D005455:Fluorescent Antibody Technique; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D005819:Genetic Markers / Q000235:genetics*; D017403:In Situ Hybridization; D051379:Mice; D008810:Mice, Inbred C57BL; D010053:Ovary / Q000166:cytology* / Q000196:embryology* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*
chemical_list: D051837:COUP Transcription Factor II; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors; C498893:Foxl2 protein, mouse; D005819:Genetic Markers; C493597:Lgr5 protein, mouse; C497587:Nr2f2 protein, mouse; D043562:Receptors, G-Protein-Coupled
keywords: Foxl2; Lgr5; Nr2f2; Ovary; Rspo1; Wnt4