Similar Datasets
Project description:β-Catenin is a regulator of cutaneous wound repair. The expression of genes that are modulated in response to changes in β-Catenin levels (stabilization and downregulation) in cutaneous mouse wounds, post injury, during the proliferative phase of repair, was investigated. We are particularly interested in genes that are modulated (in opposite directions) in response to both the induction (stabilization) versus downregulation of β-Catenin. To investigate this, conditional β-Catenin stabilized (Harada, N., et al. EMBO J. 1999 Nov 1;18(21):5931-42) mice were injected with either a Cre-expressing adenovirus, or a GFP-expressing control virus, three days following injury, and wounds were harvested eight days post injury. For conditional knockdown of β-Catenin, mice generated from a cross between conditional β-Catenin knockdown mice (Brault, V. et al., Development. 2001 Apr;128(8):1253-64), and mice that express a tamoxifen-inducible form of Cre (Hayashi, S., and McMahon, A.P., Dev Biol. 2002 Apr 15;244(2):305-18), were treated with Tamoxifen for five days, beginning at the third day after injury. Wounds were harvested eight days after wounding. This provides insight into the identities of genes modulated in response to changes in β-Catenin levels during the proliferative stage of cutaneous wound repair.
2018-12-31 | GSE50153 | GEO
Project description:β-Catenin is a regulator of cutaneous wound repair. The expression of genes that are modulated in response to changes in β-Catenin levels initiated prior to injury was investigated during the proliferative phase of repair. We are particularly interested in genes that are modulated (in opposite directions) in response to both the induction ('stabilization') versus downregulation of β-Catenin. To investigate this, conditional β-Catenin stabilized mice (Harada, N., et al. EMBO J. 1999 Nov 1;18(21):5931-42) were injected with either a Cre-expressing adenovirus, or a GFP-expressing control virus, four days prior to injury, and wounds were harvested eight days following injury. For conditional knockdown of β-Catenin, mice generated from a cross between conditional β-Catenin knockdown mice (Brault, V. et al., Development. 2001 Apr;128(8):1253-64), and mice that express a tamoxifen-inducible form of Cre (Hayashi, S., and McMahon, A.P., Dev Biol. 2002 Apr 15;244(2):305-18), were treated with Tamoxifen for five days prior to injury. Wounds were harvested eight days after wounding. This provides insight into gene expression changes that occur during the proliferative stage of cutaneous wound repair in response to changes in β-Catenin levels initiated before/at the time of injury.
2018-12-31 | GSE50152 | GEO
Project description:Gene expression in mouse whole proliferative phase wounds in response to alterations in β-Catenin levels
| PRJNA216913 | ENA
Project description:The inability of the adult mammalian heart to regenerate represents a fundamental barrier in heart failure management. In contrast, the neonatal heart retains a transient regenerative capacity, but the underlying mechanisms are not fully understood. Wnt/β-catenin signaling has been suggested as a key cardio-regenerative pathway. Here, we show that Wnt/β-catenin signaling potentiates neonatal mouse cardiomyocyte proliferation in vivo and immature human pluripotent stem cell-derived cardiomyocyte (hPSC-CM) proliferation in vitro. In contrast, Wnt/β-catenin signaling in adult mice is cardioprotective but fails to induce cardiomyocyte proliferation. Transcriptional profiling of neonatal mouse and hPSC-CM revealed a core Wnt/β-catenin-dependent transcriptional network governing cardiomyocyte proliferation. In contrast, β-catenin failed to re-engage this proliferative gene network in the adult heart, which instead reverted to a neonatal-like glycolytic program. These findings suggest that Wnt/β-catenin drives distinct transcriptional networks in regenerative and non-regenerative cardiomyocytes, which may contribute towards the inability of the adult heart to regenerate following injury.
2020-11-04 | GSE150521 | GEO
Project description:β-Catenin is an important component of the Wnt signalling pathway. As dysregulation or mutation of this pathway causes many diseases, including cancer, the β-Catenin level is carefully regulated by the destruction complex in the Wnt signalling pathway. However, the mechanisms underlying the regulation of β-Catenin ubiquitination and degradation remain unclear. Here, we find that WNK (With No Lysine [K]) kinase is a potential regulator of the Wnt signalling pathway. We show that WNK protects the interaction between β-Catenin and the Glucose-Induced degradation Deficient (GID) complex, which includes an E3 ubiquitin ligase targeting β-Catenin, and that WNK regulates the β-Catenin level. Furthermore, we show that WNK inhibitors induced β-Catenin degradation and that one of these inhibitors suppressed xenograft tumour development in mice. These results suggest that WNK is a previously unrecognized regulator of β-Catenin and a therapeutic target of cancer.
| S-EPMC7665214 | biostudies-literature
Project description:The canonical Wnt/β-catenin pathway is an essential component of multiple developmental processes. To investigate the role of this pathway in the ectoderm during facial morphogenesis, we generated conditional β-catenin mouse mutants using a novel ectoderm-specific Cre recombinase transgenic line. Our results demonstrate that ablating or stabilizing β-catenin in the embryonic ectoderm causes dramatic changes in facial morphology. There are accompanying alterations in the expression of Fgf8 and Shh, key molecules that establish a signaling center critical for facial patterning, the frontonasal ectodermal zone (FEZ). These data indicate that Wnt/β-catenin signaling within the ectoderm is critical for facial development and further suggest that this pathway is an important mechanism for generating the diverse facial shapes of vertebrates during evolution.
| S-EPMC3057077 | biostudies-literature
Project description:Wnt/β-catenin signaling, a highly conserved pathway through evolution, regulates key cellular functions including proliferation, differentiation, migration, genetic stability, apoptosis, and stem cell renewal. The Wnt pathway mediates biological processes by a canonical or noncanonical pathway, depending on the involvement of β-catenin in signal transduction. β-catenin is a core component of the cadherin protein complex, whose stabilization is essential for the activation of Wnt/β-catenin signaling. As multiple aberrations in this pathway occur in numerous cancers, WNT-directed therapy represents an area of significant developmental therapeutics focus. The recently described role of Wnt/β-catenin pathway in regulating immune cell infiltration of the tumor microenvironment renewed the interest, given its potential impact on responses to immunotherapy treatments. This article summarizes the role of Wnt/β-catenin pathway in cancer and ongoing therapeutic strategies involving this pathway.
| S-EPMC5420131 | biostudies-literature
Project description:β-catenin drives distinct transcriptional networks in proliferative and non-proliferative cardiomyocytes
| PRJNA632627 | ENA
Project description:Pulmonary carcinoids, distinct in typical and atypical, represent 2-5% of all primary lung tumors. The aim of this study was to investigate the molecular alterations correlated with the development of this form of neoplasms. A collection of 38 paraffin-embedded apparently sporadic carcinoids was investigated, through a combined study, for protein expression/localization of menin, p53, β-catenin and E-cadherin and for mutational analysis of the MEN1, TP53 and CTNNB1 genes. Menin was expressed in 71% of cases, with a prevalent cytoplasmic (c) localization, β-catenin was expressed in 68.4% of cases, of which 36.8% with a membranous (m) and 31.6% with a cytoplasmic localization. Membranous E-cadherin immunoreactivity was detected in 84.2% cases, nuclear p53 expression in 5.3% of cases. Positive correlation was found between c-menin and c-β-catenin expression (rho=0.439, P=0.008). In addition, m-β-catenin showed a positive correlation with both c-β-catenin and E-cadherin expression (rho=0.380, P=0.022 and rho=0.360, P=0.040, respectively). With regard to the E-cadherin/β-catenin complex, we found also a significant positive correlation between c-menin and 'disarrayed' β-catenin expression (rho=0.481, P=0.007). MEN1 gene variants were characterized in 34% of cases. c-menin was more highly expressed in tumors with MEN1 variants, compared to tumors without MEN1 variants (P=0.023). Three nucleotide variants of TP53 were also detected. This study confirms the involvement of the MEN1 gene in the development of sporadic pulmonary carcinoids, demonstrates the accumulation of menin in the cytoplasm, and indicates that the disarrayed pattern of the complex significantly correlates with c-menin accumulation.
| S-EPMC3583815 | biostudies-literature
Project description:Formation of a functional kidney depends on the balance between renewal and differentiation of nephron progenitors. Failure to sustain this balance can lead to kidney failure or stem cell tumors. For nearly 60 years, we have known that signals from an epithelial structure known as the ureteric bud were essential for maintaining this balance. More recently it was discovered that one molecule, Wnt9b, was necessary for both renewal and differentiation of the nephron progenitor cells. How one ligand signaling through one transcription factor promoted two seemingly contradictory cellular processes was unclear. In this study, we show that Wnt9b/beta-catenin signaling alone is sufficient to promote both renewal and differentiation. Moreover, we show that discrete levels of beta-catenin can promote these two disparate fates, with low levels fostering progenitor renewal and high levels driving differentiation. These results provide insight into how Wnt9b regulates distinct target genes that balance nephron progenitor renewal and differentiation.
| S-EPMC5988999 | biostudies-literature