Building Pathways for Ovary Organogenesis in the Mouse Embryo

Department of Veterinary Biosciences, University of Illinois at Urbana-Champaign, Illinois, USA.
Current Topics in Developmental Biology (Impact Factor: 4.68). 01/2010; 90:263-90. DOI: 10.1016/S0070-2153(10)90007-0
Source: PubMed


Despite its significant role in oocyte generation and hormone production in adulthood, the ovary, with regard to its formation, has received little attention compared to its male counterpart, the testis. With the exception of germ cells, which undergo a female-specific pattern of meiosis, morphological changes in the fetal ovary are subtle. Over the past 40 years, a number of hypotheses have been proposed for the organogenesis of the mammalian ovary. It was not until the turn of the millennium, thanks to the advancement of genetic and genomic approaches, that pathways for ovary organogenesis that consist of positive and negative regulators have started to emerge. Through the action of secreted factors (R-spondin1, WNT4, and follistatin) and transcription regulators (beta-catenin and FOXL2), the developmental fate of the somatic cells is directed toward ovarian, while testicular components are suppressed. In this chapter, we review the history of studying ovary organogenesis in mammals and present the most recent discoveries using the mouse as the model organism.

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Available from: Humphrey Hung-Chang Yao, Mar 17, 2014
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    • "While there are elegant reviews of germ-line cyst breakdown , primordial follicle formation, the onset of follicle activation, and cellÀcell communication during antral follicle development (e.g., Albertini et al., 2001; Pepling, 2006, 2012; Edson et al., 2009; Su et al., 2009; Trombly et al., 2009a; Binelli and Murphy, 2010; Liu et al., 2010a; Jagarlamudi and Rajkovic, 2012; Sanchez and Smitz, 2012), the remainder of this review will focus on a specific cadre of factors that have the unique properties of being present throughout the duration of germ-line cyst formation to establishment of primordial follicles, in addition to clearly playing a role in survival of early stage follicles. Their known activities support the hypothesis that the foundation of folliculogenesis begins at the onset of ovarian cord formation , coinciding with transition to the oocyte fate, and requires cooperation between both germ cells and somatic cells (Eppig, 1991; Byskov et al., 1997; Lei et al., 2006; Qing et al., 2008; Nicholas et al., 2010). "
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    ABSTRACT: The ovary functions to chaperone the most precious cargo for female individuals, the oocyte, thereby allowing the passage of genetic material to subsequent generations. Within the ovary, single oocytes are surrounded by a legion of granulosa cells inside each follicle. These two cell types depend upon one another to support follicle formation and oocyte survival. The infrastructure and events that work together to ultimately form these functional follicles within the ovary are unprecedented, given that the oocyte originates as a cell like all other neighboring cells within the embryo prior to gastrulation. This review discusses the journey of the germ cell in the context of the developing female mouse embryo, with a focus on specific signaling events and cell-cell interactions that escort the primordial germ cell as it is specified into the germ cell fate, migrates through the hindgut into the gonad, differentiates into an oocyte, and culminates upon formation of the primordial and then primary follicle. Mol. Reprod. Dev. 2013. © 2013 Wiley Periodicals, Inc.
    Preview · Article · Dec 2013 · Molecular Reproduction and Development
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    • "Beginning with the generation of the Wnt4 mutation over 10 years ago (Vainio et al., 1999), canonical Wnt signaling has emerged as the predominant pathway controlling ovarian development (Chassot et al., 2008a; Tevosian and Manuylov, 2008; Liu et al., 2010a). While loss of several sex-determining genes in the XY gonad, including Sry, Sox9, or Fgf9, leads to male-to-female sex reversal, no single gene mutation leads to primary female-to-male sex reversal in the XX gonad (reviewed in Eggers and Sinclair (2012)). "
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    ABSTRACT: 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.
    Preview · Article · Sep 2013 · Developmental Biology
    • "Because of their important roles in initiating male or female gonadal development in mammals, the respective implications of either Dmrt1 or Foxl2 transcription factors were examined. Further on, two of the major signaling pathways central for early gonadal induction and maintenance in mammals, namely the canonical Hedgehog and Wnt4/β-catenin signaling pathways (Wilhelm et al. 2007; Liu et al. 2010; Franco and Yao 2012), were investigated. "
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    ABSTRACT: Genetic control of male or female gonad development displays between different groups of organisms a remarkable diversity of “master sex-determining genes” at the top of the genetic hierarchies, whereas downstream components surprisingly appear to be evolutionarily more conserved. Without much further studies, conservation of sequence has been equalized to conservation of function. We have used the medaka fish to investigate the generality of this paradigm. In medaka, the master male sex-determining gene is dmrt1bY, a highly conserved downstream regulator of sex determination in vertebrates. To understand its function in orchestrating the complex gene regulatory network, we have identified targets genes and regulated pathways of Dmrt1bY. Monitoring gene expression and interactions by transgenic fluorescent reporter fish lines, in vivo tissue-chromatin immunoprecipitation and in vitro gene regulation assays revealed concordance but also major discrepancies between mammals and medaka, notably amongst spatial, temporal expression patterns and regulations of the canonical Hedgehog and R-spondin/Wnt/Follistatin signaling pathways. Examination of Foxl2 protein distribution in the medaka ovary defined a new subpopulation of theca cells, where ovarian-type aromatase transcriptional regulation appears to be independent of Foxl2. In summary, these data show that the regulation of the downstream regulatory network of sex determination is less conserved than previously thought.
    No preview · Article · Jul 2013 · Molecular Biology and Evolution
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