Minireview: Roles of the Forkhead Transcription Factor FOXL2 in Granulosa Cell Biology and Pathology

Pisarska, Margareta D.; Barlow, Gillian; Kuo, Fang-Ting

doi:10.1210/en.2010-1041

Cited by 92 publications

(70 citation statements)

References 117 publications

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“…Numerous studies have indicated that the forkhead transcription factor FOXL2 is an essential player in ovarian development and maintenance in a variety of species [Pisarska et al, 2011]. Nevertheless, variations in the phenotype of FOXL2 mutants from species to species mean that FOXL2 may have numerous functions during ovarian development, which differ between species.…”

Section: The Foxl2-aromatase Pathwaymentioning

confidence: 99%

“…This is mainly due to a very short proline-alanine-rich region, and the absence of both the alanine-glycine-rich region and the polyalanine tract that are highly conserved in mammals [Govoroun et al, 2004]. It appears that mammalian FOXL2 has undergone expansion of these regions, which may play an important role in transcriptional repression discussed in Govoroun et al [2004] and Pisarska et al [2011] indicating that this expansion has promoted the acquisition of new functions in mammals [Mortlock et al, 2000].…”

Section: Foxl2 and Ovarian Development In Chickenmentioning

confidence: 99%

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The Molecular Genetics of Ovarian Differentiation in the Avian Model

Ayers

Sinclair²,

Smith³

2012

Sex Dev

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In birds as in mammals, sex is determined at fertilization by the inheritance of sex chromosomes. However, sexual differentiation – development of a male or female phenotype – occurs during embryonic development. Sex differentiation requires the induction of sex-specific developmental pathways in the gonads, resulting in the formation of ovaries or testes. Birds utilize a different sex chromosome system to that of mammals, where females are the heterogametic sex (carrying Z and W chromosomes), while males are homogametic (carrying 2 Z chromosomes). Therefore, while some genes essential for testis and ovarian development are conserved, important differences also exist. Namely, the key mammalian male-determining factor SRY does not exist in birds, and another transcription factor, DMRT1, plays a central role in testis development. In contrast to our understanding of testis development, ovarian differentiation is less well-characterized. Given the presence of a female-specific chromosome, studies in chicken will provide insight into the induction and function of female-specific gonadal pathways. In this review, we discuss sexual differentiation in chicken embryos, with emphasis on ovarian development. We highlight genes that may play a conserved role in this process, and discuss how interaction between ovarian pathways may be regulated.

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Section: The Foxl2-aromatase Pathwaymentioning

confidence: 99%

Section: Foxl2 and Ovarian Development In Chickenmentioning

confidence: 99%

The Molecular Genetics of Ovarian Differentiation in the Avian Model

Ayers

Sinclair²,

Smith³

2012

Sex Dev

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“…The second major development has been the discovery and characterisation of animal microRNAs (miRNAs) as key global post-transcriptional regulators of tissue growth and differentiation both in health and disease (Ambros 2004, Croce 2009, Sayed & Abdellatif 2011. Although clear advances have been made in understanding transcriptional gene regulation during follicular and luteal development (Wu & Wiltbank 2002, Liu et al 2009, Patel et al 2009, Pisarska et al 2011, little is known about the post-transcriptional mechanisms involved. Given the dynamic nature of the mammalian ovary, miRNAs are predicted to play important roles in the regulation of ovarian function, and studies over the past 5 years have already begun to identify and characterise such roles.…”

Section: Introductionmentioning

confidence: 99%

Involvement of miRNAs in ovarian follicular and luteal development

Donadeu¹,

Schauer²,

Sontakke³

2012

Journal of Endocrinology

157

106

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Although much progress has been made in the genetic dissection of biological networks involved in follicular/luteal development in the mammalian ovary, the gene regulation mechanisms involved are still poorly understood. Over the last 10 years, miRNAs have emerged as master regulators of tissue growth and differentiation in animals. However, compared with other body tissues, little is still known about the functional involvement of miRNAs in the ovary. Several studies have identified miRNA populations specifically associated with the development of follicles and corpora lutea, particularly in relation to the follicular-luteal transition, and the functional involvement of some of these miRNAs has been characterised in vitro and/or in vivo. Specifically, three different miRNAs, miR-224, miR-378 and miR-383, have shown to be involved in regulating aromatase expression during follicle development. In addition, miR-21 has been identified as promoting follicular cell survival during ovulation, and pro-angiogenic miR-17-5p and let-7b were shown to be necessary for normal development of the corpus luteum. Experimental evidence for the involvement of several other miRNAs in different aspects of follicle/luteal development has also been obtained. In addition, many of these studies exemplify the challenges associated with identifying physiologically relevant targets of ovarian miRNAs. Continuous advances in this field will be considerably facilitated by progress in understanding miRNA physiology in other body systems and will eventually lead to a much better understanding of the control of follicular/luteal development. In turn, through the potential offered by miRNA diagnostics and miRNA therapeutics, this new knowledge should bring considerable benefits to reproductive medicine.

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“…Among all these genes, Foxl2 has attracted particular attention during the last 15 years as a key player due to its involvement in sex differentiation and oogenesis [Baron et al, 2005;Benayoun et al, 2009;Veitia, 2010;Boulanger et al, 2014;Georges et al, 2014a;Nicol and Yao, 2014]. A substantial amount of information on FOXL2 action was initially acquired from studies in humans and other mammals, and many excellent reviews have already been published, most centered on the roles of FOXL2 in normal or pathological female development in mammals and/or vertebrates [Fuhrer, 2002;Baron et al, 2005;De Baere et al, 2005;Benayoun et al, 2009Benayoun et al, , 2010Beysen et al, 2009;Kobel et al, 2009;Pisarska et al, 2011;Uhlenhaut and Treier, 2011;Biason-Lauber, 2012;Caburet et al, 2012;Verdin and De Baere, 2012;Takahashi et al, 2013;Georges et al, 2014a;Rosario et al, 2014;Leung et al, 2016]. The present review focuses on ' foxl2 ' genes in light of recent findings on their evolution, expression, and roles in sex differentiation in animals.…”

mentioning

confidence: 99%

Foxl2 and Its Relatives Are Evolutionary Conserved Players in Gonadal Sex Differentiation

Bertho

Pasquier

Pan

et al. 2016

Sex Dev

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Foxl2 is a member of the large family of Forkhead Box (Fox) domain transcription factors. It emerged during the last 15 years as a key player in ovarian differentiation and oogenesis in vertebrates and especially mammals. This review focuses on Foxl2 genes in light of recent findings on their evolution, expression, and implication in sex differentiation in animals in general. Homologs of Foxl2 and its paralog Foxl3 are found in all metazoans, but their gene evolution is complex, with multiple gains and losses following successive whole genome duplication events in vertebrates. This review aims to decipher the evolutionary forces that drove Foxl2/3 gene specialization through sub- and neo-functionalization during evolution. Expression data in metazoans suggests that Foxl2/3 progressively acquired a role in both somatic and germ cell gonad differentiation and that a certain degree of sub-functionalization occurred after its duplication in vertebrates. This generated a scenario where Foxl2 is predominantly expressed in ovarian somatic cells and Foxl3 in male germ cells. To support this hypothesis, we provide original results showing that in the pea aphid (insects) foxl2/3 is predominantly expressed in sexual females and showing that in bovine ovaries FOXL2 is specifically expressed in granulosa cells. Overall, current results suggest that Foxl2 and Foxl3 are evolutionarily conserved players involved in somatic and germinal differentiation of gonadal sex.

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Minireview: Roles of the Forkhead Transcription Factor FOXL2 in Granulosa Cell Biology and Pathology

Cited by 92 publications

References 117 publications

The Molecular Genetics of Ovarian Differentiation in the Avian Model

The Molecular Genetics of Ovarian Differentiation in the Avian Model

Involvement of miRNAs in ovarian follicular and luteal development

Foxl2 and Its Relatives Are Evolutionary Conserved Players in Gonadal Sex Differentiation

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