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Dongwang Zheng, Xiaoyan Yang, Donglai Sheng, Dongliang Yu, Guoqing Liang, Luming Guo, Mei Xu, Xu Hu, Daqiang He, Yang Yang, Yuying Wang
Pou4f2 acts as a key node in the comprehensive and step-wise gene regulatory network (GRN) and regulates the development of retinal ganglion cells (RGCs). Accordingly, deletion of Pou4f2 results in RGC axon defects and apoptosis. To investigate the GRN involved in RGC regeneration, we generated a mouse line with a POU4F2-green fluorescent protein (GFP) fusion protein expressed in RGCs. Co-localization of POU4F2 and GFP in the retina and brain of Pou4f2-GFP/+ heterozygote mice was confirmed using immunofluorescence analysis...
August 17, 2016: Genesis: the Journal of Genetics and Development
Jianbo Wang, Joana Galvao, Krista M Beach, Weijia Luo, Raul A Urrutia, Jeffrey L Goldberg, Deborah C Otteson
Regenerative medicine holds great promise for the treatment of degenerative retinal disorders. Krüppel-like factors (KLFs) are transcription factors that have recently emerged as key tools in regenerative medicine because some of them can function as epigenetic reprogrammers in stem cell biology. Here, we show that KLF16, one of the least understood members of this family, is a POU4F2 independent transcription factor in retinal ganglion cells (RGCs) as early as embryonic day 15. When overexpressed, KLF16 inhibits RGC neurite outgrowth and enhances RGC growth cone collapse in response to exogenous ephrinA5 ligands...
August 26, 2016: Journal of Biological Chemistry
Aaron B Simmons, Samuel J Bloomsburg, Samuel A Billingslea, Morgan M Merrill, Shuai Li, Marshall W Thomas, Peter G Fuerst
PURPOSE: A transgenic mouse that expresses Cre recombinase under control of the Pou4f2-promoter (also referred to as Brn-3b and Brn-3.2) was characterized. Pou4f2 expression has been reported in a subset of retinal ganglion cells (RGCs) in the retina, in the midbrain, and in the germline. In this study, we characterize the expression pattern of this Cre-recombinase line and report its utility in targeted deletion, temporal deletion, RGC depletion, and germline targeting, which can be regulated by the sex of the Cre-carrying mouse...
2016: Molecular Vision
Chai-An Mao, Cavit Agca, Julie A Mocko-Strand, Jing Wang, Esther Ullrich-Lüter, Ping Pan, Steven W Wang, Maria Ina Arnone, Laura J Frishman, William H Klein
Pou domain transcription factor Pou4f2 is essential for the development of retinal ganglion cells (RGCs) in the vertebrate retina. A distant orthologue of Pou4f2 exists in the genome of the sea urchin (class Echinoidea) Strongylocentrotus purpuratus (SpPou4f1/2), yet the photosensory structure of sea urchins is strikingly different from that of the mammalian retina. Sea urchins have no obvious eyes, but have photoreceptors clustered around their tube feet disc. The mechanisms that are associated with the development and function of photoreception in sea urchins are largely unexplored...
March 16, 2016: Proceedings. Biological Sciences
Yongqiang Wang, Yuan Yu, Rui Ye, Duo Zhang, Qiaoling Li, Dan An, Lu Fang, Youcheng Lin, Yong Hou, Abai Xu, Yu Fu, Wei Lu, Xin Chen, Mingwei Chen, Meng Zhang, Huiling Jiang, Chuanxia Zhang, Pei Dong, Chong Li, Jun Chen, Guosheng Yang, Chunxiao Liu, Zhiming Cai, Fangjian Zhou, Song Wu
To develop a routine and effectual procedure of detecting bladder cancer (BlCa), an optimized combination of epigenetic biomarkers that work synergistically with high sensitivity and specificity is necessary. In this study, methylation levels of seven biomarkers (EOMES, GDF15, NID2, PCDH17, POU4F2, TCF21, and ZNF154) in 148 individuals-which including 58 urothelial cell carcinoma (UCC) patients, 20 infected urinary calculi (IUC) patients, 20 kidney cancer (KC) patients,20 prostate cancer (PC) patients, and 30 healthy volunteers (HV)-were quantified by qMSP using the urine sediment DNA...
January 19, 2016: Oncotarget
Elin Andersson, Christina M Dahmcke, Kenneth Steven, Louise K Larsen, Per Guldberg
Molecular analysis of cells from urine provides a convenient approach to non-invasive detection of bladder cancer. The practical use of urinary cell-based tests is often hampered by difficulties in handling and analyzing large sample volumes, the need for rapid sample processing to avoid degradation of cellular content, and low sensitivity due to a high background of normal cells. We present a filtration device, designed for home or point-of-care use, which enables collection, storage and shipment of urinary cells...
2015: PloS One
Fuguo Wu, Tadeusz J Kaczynski, Santhosh Sethuramanujam, Renzhong Li, Varsha Jain, Malcolm Slaughter, Xiuqian Mu
As with other retinal cell types, retinal ganglion cells (RGCs) arise from multipotent retinal progenitor cells (RPCs), and their formation is regulated by a hierarchical gene-regulatory network (GRN). Within this GRN, three transcription factors--atonal homolog 7 (Atoh7), POU domain, class 4, transcription factor 2 (Pou4f2), and insulin gene enhancer protein 1 (Isl1)--occupy key node positions at two different stages of RGC development. Atoh7 is upstream and is required for RPCs to gain competence for an RGC fate, whereas Pou4f2 and Isl1 are downstream and regulate RGC differentiation...
March 31, 2015: Proceedings of the National Academy of Sciences of the United States of America
Veijo Nurminen, Antonio Neme, Jussi Ryynänen, Sami Heikkinen, Sabine Seuter, Carsten Carlberg
The vitamin D metabolite 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) is the high affinity ligand of the transcription factor vitamin D receptor (VDR) and therefore a direct regulator of transcription. Transcriptome-wide analysis of THP-1 human monocytes had indicated more than 600 genes to be significantly (p<0.05) stimulated after 4h incubation with 1,25(OH)2D3, but only 67 of them where more than 1.5-fold up-regulated. These include the genes encoding for the transcription factors BCL6, NFE2, POU4F2 and ELF4, which are controlled by one or two VDR binding sites within their chromosomal domains...
March 2015: Biochimica et Biophysica Acta
Jun Ishii, Hanako Sato, Takuya Yazawa, Yukiko Shishido-Hara, Chie Hiramatsu, Yukio Nakatani, Hiroshi Kamma
One-third of lung malignancies demonstrate a proneural/neuroendocrine phenotype or type of differentiation. However, it has not been clearly elucidated how proneural/neuroendocrine differentiation is controlled in lung cancers. We recently demonstrated that the POU3F2 gene plays a significant role in proneural/neuroendocrine differentiation of lung cancers. Because class III POU genes (POU3F1, POU3F2, POU3F3, and POU3F4) and class IV POU genes (POU4F1, POU4F2, and POU4F3) share similar properties in neural development, we analyzed the association between class III/IV POU genes and a proneural/neuroendocrine phenotype in lung cancers using seven small cell lung cancer (SCLC) cell lines and twelve non-SCLC (NSCLC) cell lines...
September 2014: Pathology International
Zhiguang Gao, Chai-An Mao, Ping Pan, Xiuqian Mu, William H Klein
The bHLH transcription factor ATOH7 (Math5) is essential for establishing retinal ganglion cell (RGC) fate. However, Atoh7-expressing retinal progenitor cells (RPCs) can give rise to all retinal cell types, suggesting that other factors are involved in specifying RGCs. The basis by which a subpopulation of Atoh7-expressing RPCs commits to an RGC fate remains uncertain but is of critical importance to retinal development since RGCs are the earliest cell type to differentiate. To better understand the regulatory mechanisms leading to cell-fate specification, a binary genetic system was generated to specifically label Atoh7-expressing cells with green fluorescent protein (GFP)...
November 2014: Developmental Neurobiology
Liang Huang, Fang Hu, Xiaoling Xie, Jeffery Harder, Kimberly Fernandes, Xiang-yun Zeng, Richard Libby, Lin Gan
PURPOSE: To investigate the role of Pou4f1 and Pou4f2 in the survival of adult retinal ganglion cells (RGCs). METHODS: Conditional alleles of Pou4f1 and Pou4f2 were generated (Pou4f1loxP and Pou4f2loxP respectively) for the removal of Pou4f1 and Pou4f2 in adult retinas. A tamoxifen-inducible Cre was used to delete Pou4f1 and Pou4f2 in adult mice and retinal sections and flat mounts were subjected to immunohistochemistry to confirm the deletion of both alleles and to quantify the changes in the number of RGCs and other retinal neurons...
2014: PloS One
Min Deng, Hua Yang, Xiaoling Xie, Guoqing Liang, Lin Gan
POU-homeodomain and LIM-homeodomain transcription factors are expressed in developing projection neurons within retina, inner ear, dorsal root ganglion, and trigeminal ganglion, and play synergistic roles in their differentiation and survival. Here, using immunohistochemistry, we present a comparative analysis of the spatiotemporal expression pattern of POU4F1, POU4F2, and ISL1 during the development of cochleovestibular ganglion (CVG) neurons in mouse inner ear. At early stages, when otic neurons are first detected in the otic epithelium (OE) and migrate into periotic mesenchyme to form the CVG, POU4F1 and ISL1 are co-expressed in a majority of the delaminated CVG neurons, which are marked by NEUROD1 expression, but POU4F1 is absent in the otic epithelium...
May 2014: Gene Expression Patterns: GEP
Renzhong Li, Fuguo Wu, Raili Ruonala, Darshan Sapkota, Zihua Hu, Xiuqian Mu
Precise regulation of gene expression during biological processes, including development, is often achieved by combinatorial action of multiple transcription factors. The mechanisms by which these factors collaborate are largely not known. We have shown previously that Isl1, a Lim-Homeodomain transcription factor, and Pou4f2, a class IV POU domain transcription factor, co-regulate a set of genes required for retinal ganglion cell (RGC) differentiation. Here we further explore how these two factors interact to precisely regulate gene expression during RGC development...
2014: PloS One
Meeta P Pradhan, Akshay Desai, Mathew J Palakal
BACKGROUND: Epigenetics refers to the reversible functional modifications of the genome that do not correlate to changes in the DNA sequence. The aim of this study is to understand DNA methylation patterns across different stages of lung adenocarcinoma (LUAD). RESULTS: Our study identified 72, 93 and 170 significant DNA methylated genes in Stages I, II and III respectively. A set of common 34 significant DNA methylated genes located in the promoter section of the true CpG islands were found across stages, and these were: HOX genes, FOXG1, GRIK3, HAND2, PRKCB, etc...
2013: BMC Systems Biology
Yasuko Kikuchi, Eiichi Tsuji, Koichi Yagi, Keisuke Matsusaka, Shingo Tsuji, Junichi Kurebayashi, Toshihisa Ogawa, Hiroyuki Aburatani, Atsushi Kaneda
Cancer arises through accumulation of epigenetic and genetic alteration. Aberrant promoter methylation is a common epigenetic mechanism of gene silencing in cancer cells. We here performed genome-wide analysis of DNA methylation of promoter regions by Infinium HumanMethylation27 BeadChip, using 14 clinical papillary thyroid cancer samples and 10 normal thyroid samples. Among the 14 papillary cancer cases, 11 showed frequent aberrant methylation, but the other three cases showed no aberrant methylation at all...
2013: Frontiers in Genetics
Marek Pacal, Rod Bremner
BACKGROUND: Despite the disease relevance, understanding of human retinal development lags behind that of other species. We compared the kinetics of gene silencing or induction during ganglion cell development in human and murine retina. RESULTS: Induction of POU4F2 (BRN3B) marks ganglion cell commitment, and we detected this factor in S-phase progenitors that had already silenced Cyclin D1 and VSX2 (CHX10). This feature was conserved in human and mouse retina, and the fraction of Pou4f2+ murine progenitors labeled with a 30 min pulse of BrdU matched the fraction of ganglion cells predicted to be born in a half-hour period...
May 2014: Developmental Dynamics: An Official Publication of the American Association of Anatomists
Melody Shi, Sumit R Kumar, Oluwaseyi Motajo, Friedrich Kretschmer, Xiuqian Mu, Tudor C Badea
BACKGROUND: Visual information is conveyed from the retina to the brain via 15-20 Retinal Ganglion Cell (RGC) types. The developmental mechanisms by which RGC types acquire their distinct molecular, morphological, physiological and circuit properties are essentially unknown, but may involve combinatorial transcriptional regulation. Brn3 transcription factors are expressed in RGCs from early developmental stages, and are restricted in adults to distinct, partially overlapping populations of RGC types...
2013: PloS One
Jang-Hyeon Cho, Chai-An Mao, William H Klein
PURPOSE: Retinal ganglion cell (RGC) death and optic nerve degeneration are complex processes whose underlying molecular mechanisms are only vaguely understood. Treatments commonly used for optic nerve degeneration have little long-term value and only prolong degeneration. Recent advances in stem cell replacement therapy offer new ways to overcome RGC loss by transferring healthy cells into eyes of afflicted individuals. However, studies on stem cell replacement for optic nerve degeneration are hampered by limitations of the available animal models, especially genetic models...
2012: Molecular Vision
Francisco M Nadal-Nicolás, Manuel Jiménez-López, Manuel Salinas-Navarro, Paloma Sobrado-Calvo, Juan J Alburquerque-Béjar, Manuel Vidal-Sanz, Marta Agudo-Barriuso
The three members of the Pou4f family of transcription factors: Pou4f1, Pou4f2, Pou4f3 (Brn3a, Brn3b and Brn3c, respectively) play, during development, essential roles in the differentiation and survival of sensory neurons. The purpose of this work is to study the expression of the three Brn3 factors in the albino and pigmented adult rat. Animals were divided into these groups: i) untouched; ii) fluorogold (FG) tracing from both superior colliculli; iii) FG-tracing from one superior colliculus; iv) intraorbital optic nerve transection or crush...
2012: PloS One
Thomas Reinert, Michael Borre, Anders Christiansen, Gregers G Hermann, Torben F Ørntoft, Lars Dyrskjøt
BACKGROUND: Non muscle invasive bladder cancer (NMIBC) has the highest recurrence rate of any malignancy and as many as 70% of patients experience relapse. Aberrant DNA methylation is present in all bladder tumors and can be detected in urine specimens. Previous studies have identified DNA methylation markers that showed significant diagnostic value. We evaluated the significance of the biomarkers for early detection of tumor recurrence in urine. METHODOLOGY/PRINCIPAL FINDINGS: The methylation levels of EOMES, HOXA9, POU4F2, TWIST1, VIM, and ZNF154 in urine specimens were measured by real-time PCR (MethyLight)...
2012: PloS One
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