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Riikka Kivelä, Ida Salmela, Yen Hoang Nguyen, Tatiana V Petrova, Heikki A Koistinen, Zoltan Wiener, Kari Alitalo
The remarkable adaptive and regenerative capacity of skeletal muscle is regulated by several transcription factors and pathways. Here we show that the transcription factor Prox1 is an important regulator of myoblast differentiation and of slow muscle fibre type. In both rodent and human skeletal muscles Prox1 is specifically expressed in slow muscle fibres and in muscle stem cells called satellite cells. Prox1 activates the NFAT signalling pathway and is necessary and sufficient for the maintenance of the gene program of slow muscle fibre type...
October 12, 2016: Nature Communications
Bin Zhang, Sheqing Ji, Fei Ma, Qi Ma, Xianzhi Lu, Xiaobing Chen
Dysregulation of microRNAs (miRNAs) are linked to tumorigenesis and tumor progression. In this study, we examined the expression of miR-489 in gastric cancer tissues and cells. Loss- and gain-of-function experiments were done to determine the roles of miR-489 in gastric cancer cell proliferation and invasion. Bioinformatic prediction, luciferase reporter assays, and Western blot analysis were employed to identify the target gene(s) of miR-489. We found that miR-489 was significantly (P < 0.05) downregulated in human gastric cancer tissues and cell lines, compared to their non-malignant counterparts...
2016: American Journal of Cancer Research
Maciej Tarnowski, Damian Malinowski, Krzysztof Safranow, Violetta Dziedziejko, Michał Czerewaty, Andrzej Pawlik
Gestational diabetes mellitus (GDM) is a metabolic disorder that occurs during pregnancy. HHEX and PROX1 are genetic loci associated with diabetes mellitus type 2. HHEX and PROX1 play significant roles in carbohydrate intolerance and diabetes because these transcription factors may be involved in the regulation of insulin secretion and in glucose and lipid metabolism. The aim of this study was to examine the association between HHEX (rs5015480) and PROX1 (rs340874) gene polymorphisms and GDM. This study included 204 pregnant women with GDM and 207 pregnant women with the normal glucose tolerance (NGT)...
September 29, 2016: Clinical Genetics
Karyn Jourdeuil, Tamara Anne Franz-Odendaal
The induction and patterning of the conjunctival papillae (i.e. epithelial thickenings of the conjunctiva required for the induction of the underlying, neural crest-derived scleral ossicles) is complex. It takes place over a period of two days and follows a defined spatiotemporal sequence. In this study, we investigated the spatial and temporal expression pattern of four genes over seven morphological stages of development of these papillae. We show that β-catenin is expressed during the pre-patterning of the epithelium prior to papilla induction and second that β-catenin, Ednrb and Inhba are expressed during the induction and patterning of the conjunctival papillae...
September 21, 2016: Gene Expression Patterns: GEP
Pavel Hamet, Mounsif Haloui, François Harvey, François-Christophe Marois-Blanchet, Paul Simon, John Raelson, Michael Phillips, John Chalmers, Mark Woodward, Michel Marre, Stephen Harrap, Johanne Tremblay
OBJECTIVE: We have previously reported distinct genetic architectures of renal impairment in T2D patients of Slavic and Celtic origins participating in the ADVANCE trial (J Hypertens. 2015 Jun;33 Suppl 1:e3). Further analysis suggests that the major driver of the difference in the prevalence of T2D complications between Slavic and Celtic groups is due to an earlier onset of diabetes in Slavic patients. In an attempt to distinguish between environmental and genetic factors on age of onset of diabetes, we have determined the age of onset of T2D in Slavic subjects living in Celtic countries and confirmed the same earlier onset (-2 years) in these subjects, notwithstanding their living environment...
September 2016: Journal of Hypertension
Hitomi Aoki, Hajime Ogino, Hiroyuki Tomita, Akira Hara, Takahiro Kunisada
REST (RE1-silencing transcription factor, also called Nrsf) is involved in the maintenance of the undifferentiated state of neuronal stem/progenitor cells in vitro by preventing precocious expression of neuronal genes. REST expression was then decreased in developing neurons to down-regulate neuronal genes which allow their maturation. However, the function of REST during neurogenesis in vivo remains to be elucidated because of the early embryonic lethal phenotype of conventional Rest knockout mice. In order to investigate the role of REST in ocular tissues, we generated and examined the mice evoking genetic ablation to Rest specifically to neural tissues including ocular tissue...
2016: PloS One
Kenney R Roodakker, Tamador Elsir, Per-Henrik D Edqvist, Daniel Hägerstrand, Joseph Carlson, Malgorzata Lysiak, Roger Henriksson, Fredrik Pontén, Johan Rosell, Peter Söderkvist, Roger Stupp, Elena Tchougounova, Monica Nistér, Annika Malmström, Anja Smits
PROX1 is a transcription factor with an essential role in embryonic development and determination of cell fate. In addition, PROX1 has been ascribed suppressive as well as oncogenic roles in several human cancers, including brain tumors. In this study we explored the correlation between PROX1 expression and patient survival in high-grade astrocytomas. For this purpose, we analyzed protein expression in tissue microarrays of tumor samples stratified by patient age and IDH mutation status. We initially screened 86 unselected high-grade astrocytomas, followed by 174 IDH1-R132H1 immunonegative glioblastomas derived from patients aged 60 years and older enrolled in the Nordic phase III trial of elderly patients with newly diagnosed glioblastoma...
September 10, 2016: Oncotarget
Yulia Ga-Eun Lee, Gou Young Koh
BACKGROUND: Lymph node (LN) formation requires multiple but coordinated signaling from intrinsic and extrinsic cellular components during embryogenesis. However, the contribution and role of lymphatic vessels (LVs) in LN formation and maturation are poorly defined. Here, using lymphatic-specific reporters, Prox1-GFP mice and Vegfc(+/LacZ) mice, we analyzed migration, assembly, and ingrowth of lymphatic endothelial cells (LECs) in LNs during pre- and postnatal development. RESULTS: Prox1(+) LECs form string-like connections rather than lymph sac-like structures until E14...
September 13, 2016: Developmental Dynamics: An Official Publication of the American Association of Anatomists
Jian Sun, Yilin Zhao, Rebecca McGreal, Yamit Cohen-Tayar, Shira Rockowitz, Carola Wilczek, Ruth Ashery-Padan, David Shechter, Deyou Zheng, Ales Cvekl
BACKGROUND: Pax6 is a key regulator of the entire cascade of ocular lens formation through specific binding to promoters and enhancers of batteries of target genes. The promoters and enhancers communicate with each other through DNA looping mediated by multiple protein-DNA and protein-protein interactions and are marked by specific combinations of histone posttranslational modifications (PTMs). Enhancers are distinguished from bulk chromatin by specific modifications of core histone H3, including H3K4me1 and H3K27ac, while promoters show increased H3K4me3 PTM...
2016: Epigenetics & Chromatin
Mallika Pathania, Yan Wang, Vladimir N Simirskii, Melinda K Duncan
Integrins are heterodimeric cell surface molecules that mediate cell-extracellular matrix (ECM) adhesion, ECM assembly, and regulation of both ECM and growth factor induced signaling. However, the developmental context of these diverse functions is not clear. Loss of β1-integrin from the lens vesicle (mouse E10.5) results in abnormal exit of anterior lens epithelial cells (LECs) from the cell cycle and their aberrant elongation toward the presumptive cornea by E12.5. These cells lose expression of LEC markers and initiate expression of the Maf (also known as c-Maf) and Prox1 transcription factors as well as other lens fiber cell markers...
September 2, 2016: Differentiation; Research in Biological Diversity
Jingwen Wang, Yuhong Huang, Jun Zhang, Yuanyi Wei, Salma Mahoud, Ahmed Musa Hago Bakheet, Li Wang, Shuting Zhou, Jianwu Tang
Precondition for tumor lymphatic metastasis is that tumor cells induce formation of original and newborn lymphatic vessels and invade surrounding lymphatic vessels in tumor stroma, while some pathway-related molecules play an important role in mechanisms associated with proliferation and migration of lymphatic endothelial cells (LECs) and tumor cells. In lymphangiogenesis and lymphatic metastasis, the pathway-related molecules of VEGFC/D-VEGFR3/NRP2 axis, such as Furin-like enzyme, CNTN1, Prox1, LYVE-1, Podoplanin, SOX18, SDF1 and CXCR4, are direct constitutors as a portion of VEGFC/D-VEGFR3/NRP2 axis, and their biological activities rely on this ligand-receptor system...
October 1, 2016: Clinica Chimica Acta; International Journal of Clinical Chemistry
Bin Wang, Jun Huang, Jiancheng Zhou, Ke Hui, Shan Xu, Jinhai Fan, Lei Li, Xinyang Wang, Jer-Tsong Hsieh, Dalin He, Kaijie Wu
Prospero-related homeobox 1 (PROX1) is an essential regulator in lymphangiogenesis and has been implicated in both oncogenic and tumor-suppressive functions in many types of human cancers. However, the role of PROX1 in prostate cancer (PCa) remains poorly understood. In this study, based on different PCa cell lines and knockout mice, we showed that PROX1 could be suppressed by DAB2IP, a novel member of the Ras GTPase-activating protein family and a critical player in control of epithelial-mesenchymal transition (EMT) and PCa metastasis...
November 2016: Cellular Signalling
Sahar Nissim, Olivia Weeks, Jared C Talbot, John W Hedgepeth, Julia Wucherpfennig, Stephanie Schatzman-Bone, Ian Swinburne, Mauricio Cortes, Kristen Alexa, Sean Megason, Trista E North, Sharon L Amacher, Wolfram Goessling
The stepwise progression of common endoderm progenitors into differentiated liver and pancreas organs is regulated by a dynamic array of signals that are not well understood. The nuclear receptor subfamily 5, group A, member 2 gene nr5a2, also known as Liver receptor homolog-1 (Lrh-1) is expressed in several tissues including the developing liver and pancreas. Here, we interrogate the role of Nr5a2 at multiple developmental stages using genetic and chemical approaches and uncover novel pleiotropic requirements during zebrafish liver and pancreas development...
October 1, 2016: Developmental Biology
Athanasios Stergiopoulos, Panagiotis K Politis
The enormous complexity of mammalian central nervous system (CNS) is generated by highly synchronized actions of diverse factors and signalling molecules in neural stem/progenitor cells (NSCs). However, the molecular mechanisms that integrate extrinsic and intrinsic signals to control proliferation versus differentiation decisions of NSCs are not well-understood. Here we identify nuclear receptor NR5A2 as a central node in these regulatory networks and key player in neural development. Overexpression and loss-of-function experiments in primary NSCs and mouse embryos suggest that NR5A2 synchronizes cell-cycle exit with induction of neurogenesis and inhibition of astrogliogenesis by direct regulatory effects on Ink4/Arf locus, Prox1, a downstream target of proneural genes, as well as Notch1 and JAK/STAT signalling pathways...
2016: Nature Communications
Kapo Saukkonen, Jaana Hagström, Harri Mustonen, Anne Juuti, Stig Nordling, Pauliina Kallio, Kari Alitalo, Hanna Seppänen, Caj Haglund
BACKGROUND: The Wnt/β-catenin pathway has a key role in regulating cellular processes and its aberrant signaling can lead to cancer development. The role of β-catenin expression in pancreatic ductal adenocarcinoma is somewhat controversial. Transcription factor PROX1 is a target of Wnt/β-catenin signaling and it is involved in carcinogenesis through alterations in its expression. The actions can be either oncogenic or tumor suppressive depending on the tissue. The aim of this study was to investigate PROX1 and β-catenin expression in pancreatic ductal adenocarcinoma (PDAC)...
2016: BMC Cancer
Eriko Kage-Nakadai, Akane Ohta, Tomoyo Ujisawa, Simo Sun, Yoshikazu Nishikawa, Atsushi Kuhara, Shohei Mitani
The Caenorhabditis elegans (C. elegans) amphid sensory organ contains only 4 glia-like cells and 24 sensory neurons, providing a simple model for analyzing glia or neuron-glia interactions. To better characterize glial development and function, we carried out RNA interference screening for transcription factors that regulate the expression of an amphid sheath glial cell marker and identified pros-1, which encodes a homeodomain transcription factor homologous to Drosophila prospero/mammalian Prox1, as a positive regulator...
September 2016: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
Richard S Sweat, Mohammad S Azimi, Ariana D Suarez-Martinez, Prasad Katakam, Walter L Murfee
Understanding the mechanisms behind endothelial cell identity is crucial for the goal of manipulating microvascular networks. Lysophosphatidic acid (LPA) and serum stimulation have been suggested to induce a lymphatic identity in blood endothelial cells in vitro. The objective of this study was to determine if LPA or serum induces blood-to-lymphatic vessel phenotypic transition in microvascular networks. The rat mesentery culture model was used to observe the effect of stimulation on blood and lymphatic microvascular networks ex vivo...
July 2016: Physiological Reports
Trang Nguyen-Vu, Jun Wang, Fahmi Mesmar, Srijita Mukhopadhyay, Ashish Saxena, Catherine W McCollum, Jan-Åke Gustafsson, Maria Bondesson, Cecilia Williams
Colon cancer is a common cause of cancer death in the Western world. Accumulating evidence supports a protective role of estrogen via estrogen receptor beta (ERβ) but the mechanism of action is not known. Here, we elucidate a molecular mechanism whereby ERβ represses the oncogenic prospero homebox 1 (PROX1) through the upregulation of miR-205. We show that PROX1 is a potential target of miR-205 and that in clinical specimens from The Cancer Genome Atlas data, ERβ and miR-205 are decreased in colorectal cancer tissue compared to non-tumorous colon, while PROX1 levels are increased...
June 7, 2016: Oncotarget
Mingu Hong, Eunson Jung, Sara Yang, Wonhyuek Jung, Young Jin Seong, Eunkyung Park, Athanasios Bramos, Kyu Eui Kim, Sunju Lee, George Daghlian, Jung In Seo, Inho Choi, In-Seon Choi, Chester J Koh, Agnieszka Kobielak, Qi-Long Ying, Maxwell Johnson, Daniel Gardner, Alex K Wong, Dongwon Choi, Young-Kwon Hong
Several lymphatic reporter mouse lines have recently been developed to significantly improve imaging of lymphatic vessels. Nonetheless, the usage of direct visualization of lymphatic vessels has not been fully explored and documented. Here, we characterized a new Prox1-tdTomato transgenic lymphatic reporter mouse line, and demonstrated how this animal tool enables the researchers to efficiently assess developmental, surgical and pathological lymphangiogenesis by direct visualization of lymphatic vessels. Moreover, we have derived embryonic stem cells from this reporter line, and successfully differentiated them into lymphatic vessels in vivo...
2016: PloS One
Shuying He, Saima Limi, Rebecca S McGreal, Qing Xie, Lisa A Brennan, Wanda Lee Kantorow, Juraj Kokavec, Romit Majumdar, Harry Hou, Winfried Edelmann, Wei Liu, Ruth Ashery-Padan, Jiri Zavadil, Marc Kantorow, Arthur I Skoultchi, Tomas Stopka, Ales Cvekl
Ocular lens morphogenesis is a model for investigating mechanisms of cellular differentiation, spatial and temporal gene expression control, and chromatin regulation. Brg1 (Smarca4) and Snf2h (Smarca5) are catalytic subunits of distinct ATP-dependent chromatin remodeling complexes implicated in transcriptional regulation. Previous studies have shown that Brg1 regulates both lens fiber cell differentiation and organized degradation of their nuclei (denucleation). Here, we employed a conditional Snf2h(flox) mouse model to probe the cellular and molecular mechanisms of lens formation...
June 1, 2016: Development
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