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Basic helix-loop-helix transcription factor TCF21 is a downstream target of the male sex determining gene SRY.

Bhandari RK, Sadler-Riggleman I, Clement TM, Skinner MK - PLoS ONE (2011)

Bottom Line: SRY was found to directly associate with the Tcf21 promoter SRY/SOX9 response elements in vivo during fetal rat testis development.TCF21 was found to promote an in vitro sex reversal of embryonic ovarian cells to induce precursor Sertoli cell differentiation.TCF21 and SRY had similar effects on the in vitro sex reversal gonadal cell transcriptomes.

View Article: PubMed Central - PubMed

Affiliation: Center for Reproductive Biology, School of Biological Sciences, Washington State University, Pullman, Washington, United States of America.

ABSTRACT
The cascade of molecular events involved in mammalian sex determination has been shown to involve the SRY gene, but specific downstream events have eluded researchers for decades. The current study identifies one of the first direct downstream targets of the male sex determining factor SRY as the basic-helix-loop-helix (bHLH) transcription factor TCF21. SRY was found to bind to the Tcf21 promoter and activate gene expression. Mutagenesis of SRY/SOX9 response elements in the Tcf21 promoter eliminated the actions of SRY. SRY was found to directly associate with the Tcf21 promoter SRY/SOX9 response elements in vivo during fetal rat testis development. TCF21 was found to promote an in vitro sex reversal of embryonic ovarian cells to induce precursor Sertoli cell differentiation. TCF21 and SRY had similar effects on the in vitro sex reversal gonadal cell transcriptomes. Therefore, SRY acts directly on the Tcf21 promoter to in part initiate a cascade of events associated with Sertoli cell differentiation and embryonic testis development.

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Immunolocalization of TCF21 protein in embryonic testis.(A) TCF21 protein in somatic cells of the E13 testis (arrows). (B)Localization of TCF21 protein in E14 testis. Insert shows magnifiedsection of E14 testis. (C) AMH localization in E14 testis. AMH wasstained with DAB, so brown color represents Sertoli cells. (D) TCF21protein in E16 testis (green). (E) AMH localization in E16 testis.Abbreviations: GC = Germ Cells.SC = Sertoli Cells.LC = Interstitial cells. Dotted circles indicatetestis cord structures. Data are representative of a minimum of threedifferent experiments.
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pone-0019935-g002: Immunolocalization of TCF21 protein in embryonic testis.(A) TCF21 protein in somatic cells of the E13 testis (arrows). (B)Localization of TCF21 protein in E14 testis. Insert shows magnifiedsection of E14 testis. (C) AMH localization in E14 testis. AMH wasstained with DAB, so brown color represents Sertoli cells. (D) TCF21protein in E16 testis (green). (E) AMH localization in E16 testis.Abbreviations: GC = Germ Cells.SC = Sertoli Cells.LC = Interstitial cells. Dotted circles indicatetestis cord structures. Data are representative of a minimum of threedifferent experiments.

Mentions: Tcf21 expression has been detected quite early in development inthe embryonic mesoderm, showing a similar pattern to Wt1 andGata4[15]. In amicroarray analysis with rat gonadal RNA [12], relatively higher levelsof Tcf21 transcripts were found at the embryonic day 13 (E13)stage of testis development, after which levels are maintained during this stageof development (Fig. 1). Atembryonic day 13, which is equivalent to the 13 to 18 tail somites stage, TCF21was localized to somatic cells adjacent to germ cells (Fig. 2A). At E14, TCF21 immunopositive cellswere found in the Sertoli cells and at E16 in the interstitium including Leydigcells (Fig. 2, B&D). Asa positive control, AMH was used and localized to Sertoli cells (Figure 2C). The differentiallocalization of TCF21 protein at different times of sex determination suggestsdifferential functions at different periods of testis development. Expressionpatterns of TCF21 in the E13 and E14 testes indicate a transient role in Sertolicell differentiation, whereas expression at E16 in the interstitium suggests arole during later Leydig cell differentiation [14], [16].


Basic helix-loop-helix transcription factor TCF21 is a downstream target of the male sex determining gene SRY.

Bhandari RK, Sadler-Riggleman I, Clement TM, Skinner MK - PLoS ONE (2011)

Immunolocalization of TCF21 protein in embryonic testis.(A) TCF21 protein in somatic cells of the E13 testis (arrows). (B)Localization of TCF21 protein in E14 testis. Insert shows magnifiedsection of E14 testis. (C) AMH localization in E14 testis. AMH wasstained with DAB, so brown color represents Sertoli cells. (D) TCF21protein in E16 testis (green). (E) AMH localization in E16 testis.Abbreviations: GC = Germ Cells.SC = Sertoli Cells.LC = Interstitial cells. Dotted circles indicatetestis cord structures. Data are representative of a minimum of threedifferent experiments.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3101584&req=5

pone-0019935-g002: Immunolocalization of TCF21 protein in embryonic testis.(A) TCF21 protein in somatic cells of the E13 testis (arrows). (B)Localization of TCF21 protein in E14 testis. Insert shows magnifiedsection of E14 testis. (C) AMH localization in E14 testis. AMH wasstained with DAB, so brown color represents Sertoli cells. (D) TCF21protein in E16 testis (green). (E) AMH localization in E16 testis.Abbreviations: GC = Germ Cells.SC = Sertoli Cells.LC = Interstitial cells. Dotted circles indicatetestis cord structures. Data are representative of a minimum of threedifferent experiments.
Mentions: Tcf21 expression has been detected quite early in development inthe embryonic mesoderm, showing a similar pattern to Wt1 andGata4[15]. In amicroarray analysis with rat gonadal RNA [12], relatively higher levelsof Tcf21 transcripts were found at the embryonic day 13 (E13)stage of testis development, after which levels are maintained during this stageof development (Fig. 1). Atembryonic day 13, which is equivalent to the 13 to 18 tail somites stage, TCF21was localized to somatic cells adjacent to germ cells (Fig. 2A). At E14, TCF21 immunopositive cellswere found in the Sertoli cells and at E16 in the interstitium including Leydigcells (Fig. 2, B&D). Asa positive control, AMH was used and localized to Sertoli cells (Figure 2C). The differentiallocalization of TCF21 protein at different times of sex determination suggestsdifferential functions at different periods of testis development. Expressionpatterns of TCF21 in the E13 and E14 testes indicate a transient role in Sertolicell differentiation, whereas expression at E16 in the interstitium suggests arole during later Leydig cell differentiation [14], [16].

Bottom Line: SRY was found to directly associate with the Tcf21 promoter SRY/SOX9 response elements in vivo during fetal rat testis development.TCF21 was found to promote an in vitro sex reversal of embryonic ovarian cells to induce precursor Sertoli cell differentiation.TCF21 and SRY had similar effects on the in vitro sex reversal gonadal cell transcriptomes.

View Article: PubMed Central - PubMed

Affiliation: Center for Reproductive Biology, School of Biological Sciences, Washington State University, Pullman, Washington, United States of America.

ABSTRACT
The cascade of molecular events involved in mammalian sex determination has been shown to involve the SRY gene, but specific downstream events have eluded researchers for decades. The current study identifies one of the first direct downstream targets of the male sex determining factor SRY as the basic-helix-loop-helix (bHLH) transcription factor TCF21. SRY was found to bind to the Tcf21 promoter and activate gene expression. Mutagenesis of SRY/SOX9 response elements in the Tcf21 promoter eliminated the actions of SRY. SRY was found to directly associate with the Tcf21 promoter SRY/SOX9 response elements in vivo during fetal rat testis development. TCF21 was found to promote an in vitro sex reversal of embryonic ovarian cells to induce precursor Sertoli cell differentiation. TCF21 and SRY had similar effects on the in vitro sex reversal gonadal cell transcriptomes. Therefore, SRY acts directly on the Tcf21 promoter to in part initiate a cascade of events associated with Sertoli cell differentiation and embryonic testis development.

Show MeSH
Related in: MedlinePlus