Migration of mesonephric cells into the mammalian gonad depends on Sry

Capel, Blanche; Albrecht, Kenneth H.; Washburn, Linda L.; Eicher, Eva M.

doi:10.1016/s0925-4773(99)00047-7

Cited by 190 publications

(109 citation statements)

References 17 publications

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“…1 D and E). Fetal testicular cord development and growth are dependent on Sry-induced cell migration from the mesonephros into the gonad and cell proliferation (36)(37)(38). We propose that the presence of only a single functional Fog2 or Gata4 allele interferes with, but does not abolish, Sry-mediated signaling pathways involved in cell migration and proliferation, leading to attenuated testicular cord growth in B6 Fog2Ϫ/ϩ and Gata4 ki /ϩ XY B6 gonads.…”

Section: Discussionmentioning

confidence: 99%

“…The presence of the Y chromosome was determined by using a multiplex genotyping PCR assay on tissue lysate as described previously (37). The presence of the Fog2Ϫ allele was identified by using a multiplex PCR assay with a primer pair that amplified a fragment of the myogenin gene as a positive control (5Ј-TTACGTCCATCGTGGACAGCAT-3Ј and 5Ј-TGGGCT-GGGTGTTAGTCTTAT-3Ј) and a primer pair that amplified a fragment of the neomycin cassette (5Ј-CTTGGGTGGAGAG-GCTATTC-3Ј and 5Ј-AGGTGAGATGACAGGAGATC-3Ј).…”

Section: Methodsmentioning

confidence: 99%

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Correct dosage of Fog2 and Gata4 transcription factors is critical for fetal testis development in mice

Bouma

Washburn

Albrecht

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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Previous reports suggested that humans and mice differ in their sensitivity to the genetic dosage of transcription factors that play a role in early testicular development. This difference implies that testis determination might be somewhat different in these two species. We report that the Fog2 and Gata4 transcription factors are haploinsufficient for testis determination in mice. Whether gonadal sex reversal occurs depends on genetic background (i.e., modifier genes). gonadal sex reversal ͉ haploinsufficiency ͉ sex determination ͉ Sry ͉ Sox9 D uring human fetal development, differentiation of the bipotential gonads into ovaries or testes depends on the proper dosage of transcription factors. For example, the presence of only a single functional copy of the autosomal transcription factor-encoding genes SF1, SOX9, or WT1 can result in the development of XY females, and duplication of a chromosomal region containing SOX9 can lead to the development of XX males (1-5). In contrast, the proper dosage of the transcription factors Sf1, Sox9, and Wt1 appears not to affect testicular development in mice because XY mice containing only a single copy of these genes develop testes (6-9). This apparent species difference suggested that the correct dosage of gonadal sexdetermining transcription factors is necessary for normal testis development in humans, whereas mice are less sensitive to these gene dosage effects (10-12).Studies in our laboratory indicate that genetic background plays an essential role in the process of gonadal sex determination in mice. Specifically, mice of the C57BL/6J (B6) inbred strain are exceptionally sensitive to disturbances in the early events of gonad development and thus provide a genetic ''litmus test'' for identifying genes that cause sex reversal. For example, the Sry POS gene carried on the Mus domesticus poschiavinus Y chromosome causes ovarian tissue development when present in C57BL/6J (B6) mice but not in DBA/2J (D2) or (B6 ϫ D2)F1 mice (13,14), and a mutant allele of the X-linked transcription factor Dax1 (Nr0b1) causes gonadal sex reversal in B6 but not D2 or (B6 ϫ D2)F1 XY mice (15). This ''B6 sensitivity'' is even stronger if the AKR/J Y chromosome (Y AKR ) is present. For example, if B6 mice are heterozygous for the T Orl mutation, they develop testes. If the Y AKR chromosome is present, however, they develop ovaries (16,17). These findings suggest that genetic background, not species differences, could explain apparent differences in transcription factor dosage sensitivity for gonad development in XY humans and mice. The fact that not all XY humans are sex-reversed if only a single copy of a normal SF1 or WT1 allele is present (18-20) supports this possibility, as does the fact that XY males carrying a mutant SRY gene can pass this allele on to XY daughters (for review, see ref. 21).To test the hypothesis that testis determination in XY mice is sensitive to levels of transcription factor gene dosage in a genetic background-dependent manner, we conducted experiments to determine wh...

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Correct dosage of Fog2 and Gata4 transcription factors is critical for fetal testis development in mice

Bouma

Washburn

Albrecht

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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“…In mammals, the development of the male genital ridge is driven by pre-Sertoli cells which constitute the first cell line to commit to the male differentiation pathway and which are known to recruit other cell types to the male pathway through various signaling mechanisms (Martineau et al, 1997;Capel et al, 1999;Adams and McLaren, 2002;Malki et al, 2005). Characterization of the specific subset of genes differentially expressed in pre-Sertoli cells compared with the female genital ridge immediately after the moment of testicular sex determination should provide further understanding of the molecular mechanisms involved in these processes.…”

Section: Discussionmentioning

confidence: 99%

“…Following male sex determination, pre-Sertoli cells proliferate, polarize and aggregate around the germ cells to define the testes cords, which by exclusion define the interstitial spaces between the cords (Tilmann and Capel, 1999;Schmahl et al, 2000). Migration of cells into the gonad from the mesonephros (Merchant-Larios and Moreno-Mendoza, 1998;Nishino et al, 2001) or the coelomic epithelium (Karl and Capel, 1998;Schmahl et al, 2000) is subsequently induced by signals emanating from the pre-Sertoli cells (Martineau et al, 1997;Capel et al, 1999). Peritubular myoid cells surround the testes cords and cooperate with pre-Sertoli cells to deposit the basal lamina and further define the testis cords.…”

Section: Introductionmentioning

confidence: 99%

Presumptive pre‐sertoli cells express genes involved in cell proliferation and cell signalling during a critical window in early testis differentiation

Cory

Boyer

Pilon

et al. 2007

Molecular Reproduction Devel

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In mammals, the pre-Sertoli cell of the male genital ridge is the first cell type to display sex specific differentiation and differential gene expression. The genetic cascade driving the differentiationof pre-Sertoli cells and ultimately testis formationis beginning to be unravelled, but many questions remain. A better understanding of the transcriptome of pre-Sertoli cells immediately after sex determination is essential in order to further understand this differentiationprocess. A mouse model expressing Red Fluorescent Protein (RFP) under the control of a hybrid mouse/pig SRY promoter (HybSRYp-RFP) was used to purify cells from embryonic day 12.0 (e12.0) male genital ridges. To compare the transcriptomes of HybSRYp-RFP cell populations versus age matched whole female genital ridges, RNA was extracted and used to generate molecular probes that were hybridized onto Affymetrix Mouse Genome 430 2.0 microarrays. The expression of genes considered markers for pre-Sertoli cells, including Sox9, Mis, Dhh and Fgf9 were identified within the HybSRYp-RFP expressing cell population, while markers for germ cells (Oct4, SSEA-1) and endothelial cells (Ntrk3) were not identified. In contrast, markers for ovarian somatic cell expression, including Fst and Bmp2, were identified as overexpressed within the ovarian cell population. In a general fashion, genes identified as 2.5-fold over expressed in HybSRYp-RFP expressing cells coded notably for cell signalling and extra cellular proteins. The expression of Sox10, Stc2, Fgf18, Fgf13 and Wnt6 were further characterized via whole mount in situ hybridization (WISH) on male and female genital ridges between e11.5 and e14.5. Sox10, Fgf18, Fgf13 and Stc2 gene expression was detected within the male genital ridges while Wnt6 was found diffusely within both the male and female genital ridges. These data represent the earliest comprehensive microarray expression analysis of purified presumptive pre-Sertoli cells available to date. Mol. Reprod. Dev. 74: 1491-1504, 2007

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“…Sertoli cells and some of the interstitial cells derive from the proliferating coelomic epithelial cells that delaminate from the surface and migrate into the gonad (Karl and Capel, 1998). Sry also induces the migration of cells from the mesonephros into the developing gonad (Capel et al, 1999). These mesonephrically derived cells become the peritubular myoid cells, which interact with the Sertoli cells to lay down the basement membrane, thereby forming the testis cords.…”

Section: Mousementioning

confidence: 99%

Vertebrate sex determination: many means to an end

Morrish¹

2002

Reproduction

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Migration of mesonephric cells into the mammalian gonad depends on Sry

Cited by 190 publications

References 17 publications

Correct dosage of Fog2 and Gata4 transcription factors is critical for fetal testis development in mice

Correct dosage of Fog2 and Gata4 transcription factors is critical for fetal testis development in mice

Presumptive pre‐sertoli cells express genes involved in cell proliferation and cell signalling during a critical window in early testis differentiation

Vertebrate sex determination: many means to an end

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