Wnt/β‐catenin signaling enhances transcription of the CX43 gene in murine Sertoli cells

Abstract

Sertoli cells provide the nutritional and metabolic support for germ cells. Wnt/β‐catenin signaling is important for the development of the seminiferous epithelium during embryonic age, although after birth this pathway is downregulated. Cx43 gene codes for a protein that is critical during testicular development. The Cx43 promoter contains TCF/β‐catenin binding elements (TBEs) that contribute CX43 expression in different cell types and which may also be regulating the expression of this gene in Sertoli cells. In this study, we demonstrate that 42GPA9 Sertoli cells respond to treatments that result in accumulation of β‐catenin within the nucleus and in upregulation of CX43 gene transcription. β‐Catenin binds to TBEs located both upstream and downstream of the transcriptional start site (TSS). Luciferase reporter experiments revealed that TBEs located upstream of the TSS are necessary for β‐catenin‐mediated upregulation. Our results also indicate that the Wnt/β‐catenin‐dependent upregulation of the Cx43 gene in Sertoli cells is accompanied by changes in epigenetic parameters that may be directly contributing to generating a chromatin environment that facilitates the establishment of the transcriptional machinery at this promoter.

Mediterranean Pine Vole, Microtus duodecimcostatus: A Paradigm of an Opportunistic Breeder

“…We also found several GO terms related to Sertoli cell signaling involved in the regulation of spermatogenesis and the BTB dynamics (Figure 2D; Supplementary Table S6), including positive regulation of MAPK cascade (GO:0043410; p.adjust = 7.0 × 10 −3 ) [42], ERK1 and ERK2 cascade (GO:0070371; p.adjust = 4.5 × 10 −5 ; Zhang et al, 2014), phosphatidylinositol 3-kinase signaling (GO:0014065; p.adjust = 2.8 × 10 −2 ) [43] and regulation of cytosolic calcium ion concentration (GO:0051480; p.adjust = 2.7 × 10 −4 ) [44]. All these terms were also found in the GO analysis of Inact-up-DEG (Supplementary Table S8), among which we also found categories involved in the genetic control of the BTB integrity and spermatogenesis such as canonical WNT signaling pathway (GO:0060070; p.adjust = 1.8 × 10 −5 ) [45] and cellular response to transforming growth factor beta stimulus (GO:0071560; p.adjust = 1.3 × 10 −10 ) [42]. Gene-concept analysis using data from the GO analysis of all DEGs showed a very complex network in which the MAPK/ERK signaling pathway occupied the central region sharing many genes with the other categories (Figure 5d; Supplementary Figure S2).…”

CUGBP1, a crucial factor for heart regeneration in mice

“…During postnatal stage, the CUGBP1, GATA4 protein levels and Wnt/β-catenin signaling activity is downregulated after birth [ 6 , 13 , 27 ], accompanied by dramatically reduced heart regenerative capacity [ 4 ].…”

“…CUGBP1 levels was rapidly decreased after birth at P6 and GATA4 is strongly reduced at P7 [ 6 , 13 ]. Wnt/β-catenin signaling is normally suppressed postnatally [ 27 ]. This pattern of expression hints a role of CUGBP1 as regulator of Wnt/β-catenin signaling and GATA4 during heart regeneration.…”

Generation and Characterization of Immortalized Mouse Cortical Astrocytes From Wildtype and Connexin43 Knockout Mice

“…A promising area for future studies could examine the effect of the hTERT transgene and exogenous expression on the Wnt and downstream pathways through LoxP or CRISPR-Cas9 mediated excision of the transgene used in the IWCA and IKOCA cells. Importantly, the multiple cell lines characterized in this study and ability to re-express Cx43 will allow for more reliable studies through multiple lines and control for expression of Cx43 on other cell pathways [there are strong reciprocal interactions between Cx43 and Wnt pathways (van der Heyden et al, 1998;Ai et al, 2000;Hou et al, 2019;Lopez et al, 2019)].…”