Wnt9b permits the androgen action in promoting Wolffian duct
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ABSTRACT:
PROVIDER: PRJNA1187580 | ENA |
REPOSITORIES: ENA
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Project description:The Wolffian or mesonephric duct is the embryonic primordium that gives rise to the epididymis, vas deferens and seminal vesicle. The androgen action in the Wolffian duct mesenchyme during fetal development is the predominant driver for Wolffian duct maintenance which is critical for male fertility. However, the androgen’s capability of promoting Wolffian duct maintenance was completely lost in the absence of Wnt9b in mice. In this study, we followed up with this interesting phenomenon and elucidated cellular and molecular mechanisms whereby Wnt9b facilitates Wolffian duct maintenance in male embryos. Wnt9b belongs to the WNT family of secreted proteins and is expressed in the Wolffian duct epithelium. We found that the Wolffian duct degeneration in Wnt9b-/- male embryos was accompanied with decreased cell proliferation in the epithelium but not in the mesenchyme during sexual differentiation. Wnt9b deletion did not impair testicular androgen synthesis but altered expression pattern of mesenchymal androgen receptor. The percentage of androgen receptor positive cells in the mesenchyme was significantly reduced, which can be the cause of decreased epithelial proliferation. Wnt9b actions can be transduced by both β-catenin-dependent and β-catenin-independent pathways in the context of target cells. Transcriptomic analysis of E12.5 Wnt9b+/+ and Wnt9b-/- mesonephroi revealed that expression of multiple WNT/β-catenin-target genes was reduced in the absence of Wnt9b. Deletion of mesenchymal β-catenin led to caudal Wolffian duct degeneration and cystic formation in the cranial region. Taken together, our study uncovers the important WNT9B-AR signaling axis mediating the epithelial-mesenchymal interaction in Wolffian duct development.
2024-12-31 | GSE282202 | GEO
Project description:Wolffian duct maintenance and differentiation is predominantly driven by the androgen action, which is mediated by the androgen receptor (AR). It is well established that the mesenchyme indicates the fate and differentiation of epithelial cells. However, in vivo developmental requirement of mesenchymal AR in Wolffian duct development is still undefined. By designing a mesenchyme-specific Ar knockout (ARKO), we discovered that the loss of mesenchymal Ar led to the bilateral or unilateral degeneration of caudal Wolffian ducts and cystic formation at the cranial Wolffian ducts. Ex vivo culture of ARKO Wolffian ducts invariably resulted in bilateral defects, suggesting that some factor(s) originating from surrounding tissues in vivo might promote Wolffian duct survival and growth even in the absence of mesenchymal Ar. Mechanistically, we found cell proliferation was significantly reduced in both epithelial and mesenchymal compartments; but cell apoptosis was not affected. Transcriptomic analysis by RNA-seq revealed differentially expressed genes associated with morphological and cellular changes in ARKO male embryos (i.e. reduced cell proliferation and decreased number of epithelial cells). Mesenchymal differentiation into smooth muscle cells that are critical for morphogenesis was also impaired in ARKO male embryos. Taken together, our results demonstrate the crucial roles of the mesenchymal AR in Wolffian duct maintenance and morphogenesis in mice.
2024-01-10 | GSE246141 | GEO
Project description:Wolffian/epididymal duct morphogenesis highly coordinates with its specialized function of providing microenvironment for sperm maturation. Without normal development of Wolffian duct, male infertility will result. Therefore, it is important to understand the cellular and molecular mechanisms that regulated Wolffian duct morphogenesis. Our previous study showed that mediolateral intercalation of epithelial cells was a major driver of ductal elongation. In addition, radial intercalation of mesenchymal cells surrounding the duct also played roles in Wolffian duct morphogenesis, and all of these cell re-arrangements were regulated by protein tyrosine kinase 7 (PTK7), a member of the planar cell polarity (PCP) non-canonical Wnt pathway. In this study, we showed that PTK7 regulated assemblies of extracellular matrix (ECM) at the basement membrane and throughout the mesenchyme. Abnormal assembly of laminin, collagen IV, and nephronectin at the basement membrane and fibrosis-like deposition of fibrilla collagen in the interstitium were observed in Ptk7 knockout Wolffian ducts. Meanwhile, PTK7 regulated activity levels of small GTPase RAC1 and myosin II in the mesenchyme of the Wolffian duct. Activity levels of RAC1 and myosin II decreased in the Ptk7 knockout mesenchyme compared to controls. When in-vitro-cultured Wolffian ducts were treated with collagenase IV, cross-link of fibrilla collagen was reduced, Wolffian duct elongation and coiling was reduced significantly, and cyst-like bulge was developed in the epithelial duct. When Wolffian ducts were treated with RAC1 inhibitor NSC23766, fibrilla collagen in the mesenchyme was disassembled, and Wolffian duct elongation was suppressed significantly. Our finding suggested that PTK7 regulated ECM assembly in the mesenchyme likely through regulating RAC1 and myosin II activities. Dynamic assembly and remodeling of ECM were important to Wolffian duct morphogenesis.
2018-05-09 | GSE98715 | GEO
Project description:The bladder’s remarkable regenerative capacity in response to injury had been thought to reside exclusively in its basal and intermediate cells. While examining consequences of DNA methyltransferase 1 (Dnmt1) inactivation in mouse embryonic bladder epithelium, we made the surprising discovery that Wolffian duct epithelial cells also support bladder regeneration. Conditional inactivation of Dnmt1 in mouse urethral and bladder epithelium triggered widespread apoptosis, depleted basal and intermediate bladder cells and disrupted Uroplakin protein expression. These events coincided with recruitment of Wolffian duct epithelial cells into Dnmt1 mutant urethra and bladder where they were reprogrammed to express bladder markers including FOXA1, Keratin 5, P63 and Uroplakin. This is the first evidence that Wolffian duct epithelial cells can be summoned in vivo to replace damaged bladder epithelium and function as a cell reservoir for bladder regeneration.
2018-07-19 | GSE115477 | GEO
Project description:The overall goal of this project is to characterize the repertoire of miRNAs in E10.5 Tbx18-expressing peri-wolffian duct stroma cells during development. To achieve this, E10.5 peri-wolffian ducts were dissected from timed-mated Tbx18-Cre;CAG-tdTomato embryos, followed by FACS sorting based on RFP expression to enrich for Tbx18-expressing cells.
2024-05-07 | GSE174322 | GEO
Project description:In an XX embryo, the Wolffian duct regresses under the control of the mesenchymal transcription factor COUP-TFII. To understand cellular and molecular actions underlying Wolffian duct regression, we preformed transcriptomic analyses of XX mesonephroi with or without Coup-tfII and genome-wide analysis of COUP-TFII chromatin occupancy in XX mesonephroi. The integrative analysis of COUP-TFII genome-wide binding and transcriptomic analysis revealed the suppression of muscle differentiation and extracellular matrix genes by COUP-TFII and identified a group of COUP-TFII’s potential transcriptional partners in the mesenchyme that potentially facilitate Wolffian duct regression. These findings provide insights into the molecular action of COUP-TFII in the Wolffian duct mesenchyme and identify a list of biologically relevant candidate genes and pathways for future functional analyses in sexual differentiation of reproductive tracts.
2022-04-20 | GSE157836 | GEO
Project description:Precursors for the male and female reproductive tracts (also known as the Wolffian duct and the Müllerian duct) co-exist in a mammalian embryo before sexual differentiation. The Wolffian duct and Müllerian duct are surrounded by their own mesenchymes in the mesonephros, which can be distinguished by their specific expression of Gli1 and Amhr2, respectively. In the XX embryo, during sexual differentiation, the Wolffian duct degenerates. In this study, by tracking the fate of the Gli1+ Wolffian duct mesenchyme in the tamoxifen inducible genetic lineage tracing model Gli1-CreER; Rosa-Tomato, we demonstrate that the Wolffian duct mesenchyme does not regress along with the Wolffian duct epithelium in the XX embryo. Instead, the Wolffian duct mesenchyme is repurposed and becomes a unique mesenchymal population in the female reproductive tract. Profiling the transcriptomes and chromatin accessibilities of the Gli1+ Wolffian duct mesenchyme in XX and XY during sexual differentiation (E14.5 and E16.5) shows signaling pathways and transcriptional factors that potentially involves the female and male fate differentiation of the Gli1+ Wolffian duct mesenchyme. Comparing the transcriptomes between the Gli1+ Wolffian duct mesenchyme and the Amhr2+ Müllerian duct mesenchyme from the neonatal uterus reveals similarities and differences between the two mesenchymal populations in the female reproductive tract. Ex vivo ablation of the Wolffian duct mesenchyme stunted the growth of the fetal female reproductive tract. In summary, our discovery of the contribution of the Wolffian duct mesenchyme to the female reproductive tract provides new insights into our understanding of sexual differentiation of reproductive tracts.
2022-10-05 | GSE179876 | GEO
Project description:Contribution of the hedgehog-signaling pathway to Wolffian Duct development.
| PRJNA608431 | ENA
Project description:Identification of androgen-responsive genes that are influenced by the presence of a functional SHBG versus a steroid-binding-deficient SHBG mutant (SHBG S42L) in the cytoplasm of PCT cells. The hypothesis tested in the study was that SHBG enhances androgen action. Results provide important information that intracellular SHBG enhances androgen-dependent stimulation or repression in PCT cells.
2010-12-15 | GSE26058 | GEO
Project description:Small RNA-seq analysis of E10.5 Tbx18-expressing peri-wolffian duct stroma
| PRJNA729438 | ENA