Cell-autonomous action of the testis-determining gene: Sertoli cells are exclusively XY in XX ↔XY chimaeric mouse testes

Burgoyne, Paul S.; Buehr, Mia; Koopman, Peter; Rossant, Janet; McLaren, Anne

doi:10.1242/dev.102.2.443

Cited by 178 publications

(5 citation statements)

References 26 publications

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“…Anne’s work on chimaeras with Paul Burgoyne (33, 34) contributed a rich source of knowledge on the subject of gonad development, sex determination and the subsequent fertility of the gonads. These studies built on work showing that the phenotypic sex of an individual mammal is determined by the sex of its gonads, i.e.…”

Section: The Mrc’s Mammalian Development Unit London 1974–1992mentioning

confidence: 99%

“…The best starting point for an appreciation of Anne’s contribution to the study of sex determination comes from her last major review (41). In this work of fine scholarship she first sets out the comparative history of the germ cell, including her important contribution to it, namely, the earliest identification of the primordial germ cells (PGCs) by alkaline phosphatase staining (33) close to the time of their formation.…”

Section: University Of Cambridge 1992–2007mentioning

confidence: 99%

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Anne Laura Dorinthea McLaren DBE. 26 April 1927—7 July 2007

Clarke¹,

Johnson

2023

Biogr. Mems Fell. R. Soc.

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Anne McLaren DBE was born into a privileged family, which affected her future in two distinct ways. Her cut-glass accent and social confidence were advantageous reminders of this early privilege, but her unrelenting rejection of it was evident in her left-wing egalitarian political and social views and actions. Anne was among the pioneers of research into mammalian development—her experiments on embryonic and fetal development in mice led indirectly to ‘test tube’ babies and contributed to our understanding of the relative roles of soma and germ cells in generating the two sexes. However, it is not only her science for which she will be remembered; her social, educational, ethical and political activities in the cause of science were paramount. She was an articulate, logical and extraordinarily confident speaker, always unrelentingly focused and thoroughly prepared. These qualities made her a formidable member of the Warnock Committee of enquiry, which generated the internationally influential guidelines on how human-assisted reproduction should be regulated. She served for 10 years with distinction on the Human Fertilisation and Embryology Authority, the UK regulatory body that resulted from the Warnock enquiry. She was a founder member, and president, of the Association of Women in Science and Engineering. Her interests extended beyond human welfare to that of animals, and she became involved with conservation and biodiversity preservation programmes internationally. She was elected Foreign Secretary of the Royal Society, the first woman to hold this office in its 330 years.

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Section: The Mrc’s Mammalian Development Unit London 1974–1992mentioning

confidence: 99%

Section: University Of Cambridge 1992–2007mentioning

confidence: 99%

Anne Laura Dorinthea McLaren DBE. 26 April 1927—7 July 2007

Clarke¹,

Johnson

2023

Biogr. Mems Fell. R. Soc.

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“…Classically, it has been accepted that a particular genomic region located on the Y-chromosome (the testis-determining locus-Tdy or testis-determining factor-TDF) is necessary for activating the male sex determination programme (Burgoyne et al, 1988;Koopman et al, 1989). Conversely, a lack of this region, as well as anti-testis and pro-ovarian gene expression, has led to female gonadal phenotype formation.…”

Section: Sex Determination: Ovary Genesmentioning

confidence: 99%

The molecular complexity of primary ovarian insufficiency aetiology and the use of massively parallel sequencing

Laissue

2018

Molecular and Cellular Endocrinology

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“…In mice, the genital ridges are first evident at embryonic day (E) 9.5. At ~E10.5, a critical switch in gonadal development occurs in which XY gonads express the testis determining gene Sry (sex-determining region Y chromosome) (Koopman et al, 1991), initiating the differentiation of the supporting cell precursors as Sertoli rather than granulosa cells (Burgoyne et al, 1988;Albrecht and Eicher, 2001). Sertoli cell signaling is thought to control further development of the male gonad (Magre and Jost, 1984;Magre and Jost, 1991;Jost and Magre, 1988), including cell proliferation (Schmahl et al, 2000), migration of mesonephric cells into the gonad (Buehr et al, 1993;Martineau et al, 1997;Merchant-Larios and Moreno-Mendoza, 1998) and differentiation of other cell lineages (Jost et al, 1973;Byskov, 1986).…”

Section: Introductionmentioning

confidence: 99%

Gonadal differentiation, sex determination and normalSryexpression in mice require direct interaction between transcription partners GATA4 and FOG2

et al. 2002

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In mammals, Sry expression in the bipotential, undifferentiated gonad directs the support cell precursors to differentiate as Sertoli cells, thus initiating the testis differentiation pathway. In the absence of Sry, or if Sry is expressed at insufficient levels, the support cell precursors differentiate as granulosa cells, thus initiating the ovarian pathway. The molecular mechanisms upstream and downstream of Sry are not well understood. We demonstrate that the transcription factor GATA4 and its co-factor FOG2 are required for gonadal differentiation. Mouse fetuses homozygous for a null allele of Fog2 or homozygous for a targeted mutation in Gata4 (Gata4ki) that abrogates the interaction of GATA4 with FOG co-factors exhibit abnormalities in gonadogenesis. We found that Sry transcript levels were significantly reduced in XY Fog2–/– gonads at E11.5, which is the time when Sry expression normally reaches its peak. In addition, three genes crucial for normal Sertoli cell function (Sox9, Mis and Dhh) and three Leydig cell steroid biosynthetic enzymes (p450scc, 3βHSD and p450c17) were not expressed in XY Fog2–/– and Gataki/ki gonads, whereas Wnt4, a gene required for normal ovarian development, was expressed ectopically. By contrast, Wt1 and Sf1, which are expressed prior to Sry and necessary for gonad development in both sexes, were expressed normally in both types of mutant XY gonads. These results indicate that GATA4 and FOG2 and their physical interaction are required for normal gonadal development.

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Cell-autonomous action of the testis-determining gene: Sertoli cells are exclusively XY in XX ↔XY chimaeric mouse testes

Cited by 178 publications

References 26 publications

Anne Laura Dorinthea McLaren DBE. 26 April 1927—7 July 2007

Anne Laura Dorinthea McLaren DBE. 26 April 1927—7 July 2007

The molecular complexity of primary ovarian insufficiency aetiology and the use of massively parallel sequencing

Gonadal differentiation, sex determination and normalSryexpression in mice require direct interaction between transcription partners GATA4 and FOG2

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