Apcdd1

BACKGROUND: Müllerian ducts are paired embryonic tubes that give rise to the female reproductive tract in vertebrates. Many disorders of female reproduction can be attributed to anomalies of Müllerian duct development. However, the molecular genetics of Müllerian duct formation is poorly understood and most disorders of duct development have unknown etiology. In this study, we describe for the first time the transcriptional landscape of the embryonic Müllerian duct, using the chicken embryo as a model system...

We have analyzed the expression of key genes orchestrating tail regeneration in lizard under normal and scarring conditions after cauterization. At 1-day post-cauterization (1 dpc), the injured blastema contains degenerating epithelial and mesenchymal cells, numerous mast cells, and immune cells. At 3 and 7 dpc, a stratified wound epidermis is forming while fibrocytes give rise to a scarring connective tissue. Oncogenes such as wnt2b, egfl6, wnt6, and mycn and the tumor suppressor arhgap28 are much more expressed than other oncogenes (hmga2, rhov, fgf8, fgfr4, tert, shh) and tumor suppressors (apcdd1, p63, rb, fat2, bcl11b) in the normal blastema and at 7 dpc...

Cancer chemoresistance is often attributed to the presence of cancer stem cell (CSC)-like cells, but whether they are homogeneously chemoresistant remains unclear. We previously showed that in colon tumors, a subpopulation of LGR5+ CSC-like cells driven by TCF1 (TCF7), a Wnt-responsive transcription factor, were responsible for tumorigenicity. Here we demonstrate that the tumorigenic subpopulation of mouse LGR5+ cells exists in a slow-cycling state and identify a unique 22-gene signature that characterizes these slow-cycling CSC...

The hair follicle is an excellent mini-system illustrating the mechanisms governing organogenesis and regeneration. Although the general mechanisms modulating skin and hair follicle development are widely studied in mouse and chicken models, the delicate network regulating skin and hair diversity remains largely unclear. Sheep is an additional model to address the various wool characteristics observed in nature. The coarse and fine wool sheep with diverse fibers were examined to show differences in the primary wool follicle size and skin thickness...

The difference in the breeding programs and population history may have diversely shaped the genomes of Korean native cattle breeds. In the absence of phenotypic data, comparisons of breeds that have been subjected to different selective pressures can aid to identify genomic regions and genes controlling qualitative and complex traits. In this study to decipher genetic variation and identify evidence of divergent selection, 3 Korean cattle breeds were genotyped using the recently developed high-density GeneSeek Genomic Profiler F250 (GGP-F250) array...

Animal development and homeostasis depend on precise temporal and spatial intercellular signaling. Components shared between signaling pathways, generally thought to decrease specificity, paradoxically can also provide a solution to pathway coordination. Here we show that the Bone Morphogenetic Protein (BMP) and Wnt signaling pathways share Apcdd1 as a common inhibitor and that Apcdd1 is a taxon-restricted gene with novel domains and signaling functions. Previously, we showed that Apcdd1 inhibits Wnt signaling (Shimomura et al...

Despite recent improvements in management of idiopathic pulmonary arterial hypertension, mortality remains high. Understanding the alterations in the transcriptome-phenotype of the key lung cells involved could provide insight into the drivers of pathogenesis. In this study, we examined differential gene expression of cell types implicated in idiopathic pulmonary arterial hypertension from lung explants of patients with idiopathic pulmonary arterial hypertension compared to control lungs. After tissue digestion, we analyzed all cells from three idiopathic pulmonary arterial hypertension and six control lungs using droplet-based single cell RNA-sequencing...

BACKGROUND: Alopecia or hair loss is a complex polygenetic and psychologically devastating disease affecting millions of men and women globally. Since the gene annotation and environmental knowledge is limited for alopecia, a systematic analysis for the identification of candidate biomarkers is required that could provide potential therapeutic targets for hair loss therapy. RESULTS: We designed an interactive framework to perform a meta-analytical study based on differential expression analysis, systems biology, and functional proteomic investigations...

As the second most common malignant bone tumor in children and adolescents, Ewing sarcoma is initiated and exacerbated by a chimeric oncoprotein, most commonly, EWS-FLI1. In this study, we apply epigenomic analysis to characterize the transcription dysregulation in this cancer, focusing on the investigation of super-enhancer and its associated transcriptional regulatory mechanisms. We demonstrate that super-enhancer-associated transcripts are significantly enriched in EWS-FLI1 target genes, contribute to the aberrant transcriptional network of the disease, and mediate the exceptional sensitivity of Ewing sarcoma to transcriptional inhibition...

The present study aimed to investigate key long non-coding RNAs (lncRNAs) and genes, and to obtain insights into their roles in the progression of gallbladder cancer (GBC). The gene expression profile and non‑coding RNA profile of GSE62335, which included five separate GBC tissue samples and five matched adjacent gallbladder normal tissue samples, was downloaded from the Gene Expression Omnibus database. The differentially expressed lncRNAs and mRNAs in the GBC tissues were identified, following which RNA binding protein analysis was performed using starBase v2...

Coordinating angiogenesis with acquisition of tissue-specific properties in endothelial cells is essential for vascular function. In the retina, endothelial cells form a blood-retina barrier by virtue of tight junctions and low transcytosis. While the canonical Norrin/Fz4/Lrp5/6 pathway is essential for angiogenesis, vascular remodeling, and barrier maturation, how these diverse processes are coordinated remains poorly understood. Here we demonstrate that Apcdd1, a negative regulator of Wnt/β-catenin signaling, is expressed in retinal endothelial cells during angiogenesis and barrier formation...

PURPOSE: The study aimed to explore the anticancer effects of a novel proteasome inhibitor, ixazomib, on colorectal cancer (CRC) using a combined method of microarray and bioinformatics analysis. MATERIALS AND METHODS: Cell proliferation was tested by Cell Counting Kit-8 (CCK-8) assay for SW620 cells treated with different concentrations of ixazomib and different treatment times. The microarray analysis was conducted for six samples, including three samples of SW620 cells untreated with ixazomib and three samples of SW620 cells treated with ixazomib...

Osteosarcoma (OS) is the most common type of bone tumor in children and adults. However, the molecular mechanism underlying OS tumorigenesis remains unclear. Here, we report that the expression of APCDD1, a Wnt antagonist, was reduced in OS tissues and cells compared to adjacent normal tissue and osteoblast cells, respectively. Mechanistically, this was due to increased levels of methylation in the promoter region of the APCDD1 gene. Consistently, the DNA methyltransferase inhibitor 5-AZA-dC, reduced DNA methylation in the APCDD1 promoter, and restored APCDD1 expression in OS tissue and cells...

Stage II colon cancer (CC) still remains a clinical challenge with patient stratification for adjuvant therapy (AT) largely relying on clinical parameters. Prognostic biomarkers are urgently needed for better stratification. Previously, we have shown that WNT target genes AXIN2, DKK1, APCDD1, ASCL2 and LGR5 are silenced by DNA methylation and could serve as prognostic markers in stage II CC patients using methylation-specific PCR. Here, we have extended our discovery cohort AMC90-AJCC-II (N=65) and methylation was analyzed by quantitative pyrosequencing...

Impaired adipogenic differentiation during diet-induced obesity (DIO) promotes adipocyte hypertrophy and inflammation, thereby contributing to metabolic disease. Adenomatosis polyposis coli down-regulated 1 (APCDD1) has recently been identified as an inhibitor of Wnt signaling, a key regulator of adipogenic differentiation. Here we report a novel role for APCDD1 in adipogenic differentiation via repression of Wnt signaling and an epigenetic linkage between miR-130 and APCDD1 in DIO. APCDD1 expression was significantly up-regulated in mature adipocytes compared with undifferentiated preadipocytes in both human and mouse subcutaneous adipose tissues...

Adenomatosis polyposis coli downregulated 1 (APCDD1), a negative regulator of Wnt signaling, was examined to understand detailed mechanisms underlying Wnt signaling tooth development. In situ hybridization showed that Apcdd1 was expressed in the condensed mesenchyme at the bud stage, and in the inner enamel epithelium (IEE), including enamel knot (EK) at the cap stage. In vitro organ cultivation by using Apcdd1 antisense oligodeoxynucleotides was performed at E13.5 for 2 days to define the developmental functions of APCDD1 during tooth development...

Wnt signaling plays an essential role in developmental and regenerative myelination of the CNS, therefore it is critical to understand how the factors associated with the various regulatory layers of this complex pathway contribute to these processes. Recently, Apcdd1 was identified as a negative regulator of proximal Wnt signaling, however its role in oligodendrocyte (OL) differentiation and reymelination in the CNS remain undefined. Analysis of Apcdd1 expression revealed dynamic expression during OL development, where its expression is upregulated during differentiation...

In hair follicle cells APCDD1 inhibits the canonical WNT/β-Catenin pathway and its inactivation is associated with an autosomal dominant form of hair loss. We analyzed the role of APCDD1 for the osteogenic differentiation in dental follicle cells (DFCs) and identified a new and surprising function. Contrarily to hair follicle cells APCDD1 was crucial for the expression of β-Catenin and for the activity of the TCF/LEF reporter assay in DFCs. In addition, a depletion of APCDD1 inhibits the expression of osteogenic markers such as RUNX2 and decreased the matrix mineralization...

The monogenic inherited isolated alopecias comprise a group of clinically and genetically heterogeneous disorders with decreased or absent hair. Clinical classification of the isolated alopecias is based upon the onset of the disorder, the regions affected, and the structure of the hair shaft. Men and women are equally affected, and the mode of inheritance is autosomal dominant or autosomal recessive. Therapy does not exist for these rare forms of alopecia. However, molecular genetic diagnosis is possible for the identification of the genetic causes and for the specification of the recurrence risk...

Closure of an epithelium opening is a critical morphogenetic event for development. An excellent example for this process is the transient closure of embryonic eyelid. Eyelid closure requires shape change and migration of epithelial cells at the tip of the developing eyelids, and is dictated by numerous signaling pathways. Here we evaluated gene expression in epithelial cells isolated from the tip (leading edge, LE) and inner surface epithelium (IE) of the eyelid from E15.5 mouse fetuses by laser capture microdissection (LCM)...