SRY Directly Regulates the Neurotrophin 3 Promoter During Male Sex Determination and Testis Development in Rats1

Clement, Tracy M.; Bhandari, Ramji Kumar; Sadler‐Riggleman, Ingrid; Skinner, Michael K.

doi:10.1095/biolreprod.110.090282

Cited by 30 publications

(29 citation statements)

References 39 publications

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“…The ChIP-Chip arrays identified the presence of Tcf21 in the SRY ChIP [27], Figure 1. Our previous studies have also found Ntf3 a direct downstream target of SRY in the rat [26]. Both Tcf21 and Ntf3 have distinct functions in testicular morphogenesis [28], [29], [42] and were detected in the SRY ChIP-Chip assay.…”

Section: Discussionmentioning

confidence: 78%

Global Genome Analysis of the Downstream Binding Targets of Testis Determining Factor SRY and SOX9

2012

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A major event in mammalian male sex determination is the induction of the testis determining factor Sry and its downstream gene Sox9. The current study provides one of the first genome wide analyses of the downstream gene binding targets for SRY and SOX9 to help elucidate the molecular control of Sertoli cell differentiation and testis development. A modified ChIP-Chip analysis using a comparative hybridization was used to identify 71 direct downstream binding targets for SRY and 109 binding targets for SOX9. Interestingly, only 5 gene targets overlapped between SRY and SOX9. In addition to the direct response element binding gene targets, a large number of atypical binding gene targets were identified for both SRY and SOX9. Bioinformatic analysis of the downstream binding targets identified gene networks and cellular pathways potentially involved in the induction of Sertoli cell differentiation and testis development. The specific DNA sequence binding site motifs for both SRY and SOX9 were identified. Observations provide insights into the molecular control of male gonadal sex determination.

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Section: Discussionmentioning

confidence: 78%

Global Genome Analysis of the Downstream Binding Targets of Testis Determining Factor SRY and SOX9

2012

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“…Treatment with a TRKC receptor tyrphostin inhibitor, AG879, was found to inhibit seminiferous cord formation and mesonephros cell migration and also decreased the expression of Sox9, a downstream sex differentiation gene regulated by SRY (Cupp et al 2003). The action of NT3 as a chemoattractant for cell migration from the mesonephros into the developing gonad seems to be regulated by SRY via a physical interaction between SRY and the Ntf3 promoter that has been observed both in vitro and in vivo (Clement et al 2011).…”

Section: The Nt3-trkc Signaling Modulementioning

confidence: 83%

The potential roles of neurotrophins in male reproduction

Li¹,

Zhou²

2013

Reproduction

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Neurotrophins are a family of polypeptide growth factors that are required for the proliferation, differentiation, survival, and death of neuronal cells. A growing body of evidence suggests that they may have broader physiological roles in various non-neuronal tissues. The testicles are complex non-neuronal organs in which diverse cell types interact to achieve correct spermatogenesis. Both neurotrophins and their receptors have been detected in various cell types from mammalian testes, suggesting that neurotrophins may regulate or mediate intercellular communication within this organ. This review summarizes the existing data on the cellular distribution and possible biological roles of neurotrophins in the testes. The data reported in the literature indicate that neurotrophins affect somatic cell growth and spermatogenesis and imply that they play a role in regulating testicular development and male reproduction.Reproduction (2013) 145 R89-R95

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“…Rat tissue was chosen for technical reasons because of its suitability for the use with primary antibodies raised in mouse and rabbit. Embryonic XY and XX gonads were analyzed at the developmental stage 15.5 dpc, which corresponds to ϳ14 dpc in mice (37). A clear overlapping expression of KDR and WT1 was seen in the seminiferous cords of embryonic XY gonads (Fig.…”

Section: Wt1 Stimulates Kdr Expression In Embryonic Gonadsmentioning

confidence: 99%

Wilms tumor protein–dependent transcription of VEGF receptor 2 and hypoxia regulate expression of the testis-promoting gene Sox9 in murine embryonic gonads

Kirschner¹,

Sciesielski

Krueger³

et al. 2017

Journal of Biological Chemistry

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Wilms tumor protein 1 (WT1) has been implicated in the control of several genes in sexual development, but its function in gonad formation is still unclear. Here, we report that WT1 stimulates expression of , the gene encoding VEGF receptor 2, in murine embryonic gonads. We found that WT1 and KDR are co-expressed in Sertoli cells of the testes and somatic cells of embryonic ovaries. Vivo-morpholino-mediated WT1 knockdown decreased transcripts in cultured embryonic gonads at multiple developmental stages. Furthermore, WT1 bound to the promoter in the chromatin of embryonic testes and ovaries. Forced expression of the WT1(-KTS) isoform, which functions as a transcription factor, increased mRNA levels, whereas the WT1(+KTS) isoform, which acts presumably on the post-transcriptional level, did not. ChIP indicated that WT1(-KTS), but not WT1(+KTS), binds to the promoter. Treatment with the KDR tyrosine kinase inhibitor SU1498 or the KDR ligand VEGFA revealed that KDR signaling represses the testis-promoting gene in embryonic XX gonads. WT1 knockdown abrogated the stimulatory effect of SU1498-mediated KDR inhibition on expression. Exposure to 1% O to mimic the low-oxygen conditions in the embryo increased expression but did not affect mRNA levels in gonadal explants. However, incubation in 1% O in the presence of SU1498 significantly reduced transcripts in cultured testes and increased levels in ovaries. These findings demonstrate that both the local oxygen environment and WT1, which enhances expression, contribute to sex-specific expression in developing murine gonads.

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SRY Directly Regulates the Neurotrophin 3 Promoter During Male Sex Determination and Testis Development in Rats1

Cited by 30 publications

References 39 publications

Global Genome Analysis of the Downstream Binding Targets of Testis Determining Factor SRY and SOX9

Global Genome Analysis of the Downstream Binding Targets of Testis Determining Factor SRY and SOX9

The potential roles of neurotrophins in male reproduction

Wilms tumor protein–dependent transcription of VEGF receptor 2 and hypoxia regulate expression of the testis-promoting gene Sox9 in murine embryonic gonads

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