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https://www.readbyqxmd.com/read/27519885/sirt6-overexpression-improves-various-aspects-of-mouse-healthspan
#1
Asael Roichman, Yariv Kanfi, Renana Glazz, Shoshana Naiman, Uri Amit, Natalie Landa, Simon Tinman, Ilan Stein, Eli Pikarsky, Jonathan Leor, Haim Y Cohen
The extension in human lifespan in the last century results in a significant increase in incidence of age related diseases. It is therefore crucial to identify key factors that control elderly healthspan. Similar to dietary restriction, mice overexpressing the NAD(+) dependent protein deacylase SIRT6 (MOSES) live longer and have reduced IGF-1 levels. However, it is as yet unknown whether SIRT6 also affects various healthspan parameters. Here, a range of age related phenotypes was evaluated in MOSES mice. In comparison to their wild-type (WT) littermates, old MOSES mice showed amelioration of a variety of age-related disorders, including: improved glucose tolerance, younger hormonal profile, reduced age-related adipose inflammation and increased physical activity...
August 12, 2016: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/27426723/congenital-heart-diseases-and-their-association-with-the-variant-distribution-features-on-susceptibility-genes
#2
W Su, P Zhu, R Wang, Q Wu, M Wang, X Zhang, L Mei, J Tang, M Kumar, X Wang, L Su, N Dong
Congenital heart disease (CHD), one of the causes of childhood morbidity and mortality, is mainly triggered by a combination of environmental and genetic factors. Several susceptible genes, such as NKX2-5, GATA4 and TBX5, have been reported as closely related to heart and vessel development. CHD subtypes are classified into diverse clinical phenotypes, such as atrial septal defects (ASD), ventricular septal defects (VSD), tetralogy of Fallot (TOF), and Holt-Oram syndrome (HOS). Here, we summarize the associations of the genetic variants in these three genes with CHD subtypes...
July 18, 2016: Clinical Genetics
https://www.readbyqxmd.com/read/26840059/tinman-regulates-netrinb-in-the-cardioblasts-of-the-drosophila-dorsal-vessel
#3
Jamshid Asadzadeh, Niamh Neligan, Sunita G Kramer, Juan-Pablo Labrador
Morphogenesis of the Drosophila dorsal vessel (DV) shares similarities with that of the vertebrate heart. Precursors line up at both sides of the embryo, migrate towards the midline and fuse to form a tubular structure. Guidance receptors and their ligands have been implicated in this process in vertebrates and invertebrates, as have been a series of evolutionarily conserved cardiogenic transcriptional regulators including Tinman, the Drosophila homolog of the transcription factor Nkx-2.5. NetrinB (NetB), a repulsive ligand for the Unc-5 receptor is required to preserve the dorsal vessel hollow...
2016: PloS One
https://www.readbyqxmd.com/read/26356221/the-unc-5-receptor-is-directly-regulated-by-tinman-in-the-developing-drosophila-dorsal-vessel
#4
Jamshid Asadzadeh, Niamh Neligan, Judith J Canabal-Alvear, Amanda C Daly, Sunita Gupta Kramer, Juan-Pablo Labrador
During early heart morphogenesis cardiac cells migrate in two bilateral opposing rows, meet at the dorsal midline and fuse to form a hollow tube known as the primary heart field in vertebrates or dorsal vessel (DV) in Drosophila. Guidance receptors are thought to mediate this evolutionarily conserved process. A core of transcription factors from the NK2, GATA and T-box families are also believed to orchestrate this process in both vertebrates and invertebrates. Nevertheless, whether they accomplish their function, at least in part, through direct or indirect transcriptional regulation of guidance receptors is currently unknown...
2015: PloS One
https://www.readbyqxmd.com/read/26225919/the-drosophila-transcription-factors-tinman-and-pannier-activate-and-collaborate-with-myocyte-enhancer-factor-2-to-promote-heart-cell-fate
#5
TyAnna L Lovato, Cheryl A Sensibaugh, Kirstie L Swingle, Melody M Martinez, Richard M Cripps
Expression of the MADS domain transcription factor Myocyte Enhancer Factor 2 (MEF2) is regulated by numerous and overlapping enhancers which tightly control its transcription in the mesoderm. To understand how Mef2 expression is controlled in the heart, we identified a late stage Mef2 cardiac enhancer that is active in all heart cells beginning at stage 14 of embryonic development. This enhancer is regulated by the NK-homeodomain transcription factor Tinman, and the GATA transcription factor Pannier through both direct and indirect interactions with the enhancer...
2015: PloS One
https://www.readbyqxmd.com/read/25704510/the-myogenic-repressor-gene-holes-in-muscles-is-a-direct-transcriptional-target-of-twist-and-tinman-in-the-drosophila-embryonic-mesoderm
#6
Jennifer A Elwell, TyAnna L Lovato, Melanie M Adams, Erica M Baca, Thai Lee, Richard M Cripps
Understanding the regulatory circuitry controlling myogenesis is critical to understanding developmental mechanisms and developmentally-derived diseases. We analyzed the transcriptional regulation of a Drosophila myogenic repressor gene, Holes in muscles (Him). Previously, Him was shown to inhibit Myocyte enhancer factor-2 (MEF2) activity, and is expressed in myoblasts but not differentiating myotubes. We demonstrate that different phases of Him embryonic expression arises through the actions of different enhancers, and we characterize the enhancer required for its early mesoderm expression...
April 15, 2015: Developmental Biology
https://www.readbyqxmd.com/read/25267295/cdc42-and-formin-activity-control-non-muscle-myosin-dynamics-during-drosophila-heart-morphogenesis
#7
Georg Vogler, Jiandong Liu, Timothy W Iafe, Ede Migh, József Mihály, Rolf Bodmer
During heart formation, a network of transcription factors and signaling pathways guide cardiac cell fate and differentiation, but the genetic mechanisms orchestrating heart assembly and lumen formation remain unclear. Here, we show that the small GTPase Cdc42 is essential for Drosophila melanogaster heart morphogenesis and lumen formation. Cdc42 genetically interacts with the cardiogenic transcription factor tinman; with dDAAM which belongs to the family of actin organizing formins; and with zipper, which encodes nonmuscle myosin II...
September 29, 2014: Journal of Cell Biology
https://www.readbyqxmd.com/read/25232154/identification-of-a-novel-rna-virus-lethal-to-tilapia
#8
Marina Eyngor, Rachel Zamostiano, Japhette Esther Kembou Tsofack, Asaf Berkowitz, Hillel Bercovier, Simon Tinman, Menachem Lev, Avshalom Hurvitz, Marco Galeotti, Eran Bacharach, Avi Eldar
Tilapines are important for the sustainability of ecological systems and serve as the second most important group of farmed fish worldwide. Significant mortality of wild and cultured tilapia has been observed recently in Israel. The etiological agent of this disease, a novel RNA virus, is described here, and procedures allowing its isolation and detection are revealed. The virus, denominated tilapia lake virus (TiLV), was propagated in primary tilapia brain cells or in an E-11 cell line, and it induced a cytopathic effect at 5 to 10 days postinfection...
December 2014: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/25051213/gene-expression-function-and-diversity-of-nkx2-4-in-the-rainbow-trout-oncorhynchus-mykiss
#9
Youji Uemae, Joe Sakamoto, Yoshie Hidaka, Ai Hiratsuka, Takao Susa, Yukio Kato, Masakazu Suzuki
Nkx2 homeodomain transcription factors are involved in various developmental processes and cell specification: e.g. in mammals, NKX2-1 is essential for thyroid-specific gene expression and thyroid morphogenesis. Among Nkx2 proteins, information is still very limited for Nkx2-4. In the present study, we have identified three distinct cDNAs encoding Nkx2-4 isoforms (Nkx2-4a, -b, and -c) from the rainbow trout thyroid tissue, and characterized their transcriptional properties. The trout Nkx2-4 proteins were all predicted to conserve three characteristic domains: the tinman-like amino terminal decapeptide, the NK2 homeodomain, and the NK2-specific domain, and also share 75-89% amino acid similarity...
September 15, 2014: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/24949939/cdc42-is-required-in-a-genetically-distinct-subset-of-cardiac-cells-during-drosophila-dorsal-vessel-closure
#10
David Swope, Joseph Kramer, Tiffany R King, Yi-Shan Cheng, Sunita G Kramer
The embryonic heart tube is formed by the migration and subsequent midline convergence of two bilateral heart fields. In Drosophila the heart fields are organized into two rows of cardioblasts (CBs). While morphogenesis of the dorsal ectoderm, which lies directly above the Drosophila dorsal vessel (DV), has been extensively characterized, the migration and concomitant fundamental factors facilitating DV formation remain poorly understood. Here we provide evidence that DV closure occurs at multiple independent points along the A-P axis of the embryo in a "buttoning" pattern, divergent from the zippering mechanism observed in the overlying epidermis during dorsal closure...
August 15, 2014: Developmental Biology
https://www.readbyqxmd.com/read/23922708/contribution-of-distinct-homeodomain-dna-binding-specificities-to-drosophila-embryonic-mesodermal-cell-specific-gene-expression-programs
#11
Brian W Busser, Stephen S Gisselbrecht, Leila Shokri, Terese R Tansey, Caitlin E Gamble, Martha L Bulyk, Alan M Michelson
Homeodomain (HD) proteins are a large family of evolutionarily conserved transcription factors (TFs) having diverse developmental functions, often acting within the same cell types, yet many members of this family paradoxically recognize similar DNA sequences. Thus, with multiple family members having the potential to recognize the same DNA sequences in cis-regulatory elements, it is difficult to ascertain the role of an individual HD or a subclass of HDs in mediating a particular developmental function. To investigate this problem, we focused our studies on the Drosophila embryonic mesoderm where HD TFs are required to establish not only segmental identities (such as the Hox TFs), but also tissue and cell fate specification and differentiation (such as the NK-2 HDs, Six HDs and identity HDs (I-HDs))...
2013: PloS One
https://www.readbyqxmd.com/read/23326246/genome-wide-screens-for-in-vivo-tinman-binding-sites-identify-cardiac-enhancers-with-diverse-functional-architectures
#12
Hong Jin, Robert Stojnic, Boris Adryan, Anil Ozdemir, Angelike Stathopoulos, Manfred Frasch
The NK homeodomain factor Tinman is a crucial regulator of early mesoderm patterning and, together with the GATA factor Pannier and the Dorsocross T-box factors, serves as one of the key cardiogenic factors during specification and differentiation of heart cells. Although the basic framework of regulatory interactions driving heart development has been worked out, only about a dozen genes involved in heart development have been designated as direct Tinman target genes to date, and detailed information about the functional architectures of their cardiac enhancers is lacking...
2013: PLoS Genetics
https://www.readbyqxmd.com/read/22949613/tup-islet1-integrates-time-and-position-to-specify-muscle-identity-in-drosophila
#13
Hadi Boukhatmi, Jean Louis Frendo, Jonathan Enriquez, Michèle Crozatier, Laurence Dubois, Alain Vincent
The LIM-homeodomain transcription factor Tailup/Islet1 (Tup) is a key component of cardiogenesis in Drosophila and vertebrates. We report here an additional major role for Drosophila Tup in specifying dorsal muscles. Tup is expressed in the four dorsal muscle progenitors (PCs) and tup-null embryos display a severely disorganized dorsal musculature, including a transformation of the dorsal DA2 into dorsolateral DA3 muscle. This transformation is reciprocal to the DA3 to DA2 transformation observed in collier (col) mutants...
October 2012: Development
https://www.readbyqxmd.com/read/22276214/spire-an-actin-nucleation-factor-regulates-cell-division-during-drosophila-heart-development
#14
Peng Xu, Tamara L Johnson, Jessica R Stoller-Conrad, Robert A Schulz
The Drosophila dorsal vessel is a beneficial model system for studying the regulation of early heart development. Spire (Spir), an actin-nucleation factor, regulates actin dynamics in many developmental processes, such as cell shape determination, intracellular transport, and locomotion. Through protein expression pattern analysis, we demonstrate that the absence of spir function affects cell division in Myocyte enhancer factor 2-, Tinman (Tin)-, Even-skipped- and Seven up (Svp)-positive heart cells. In addition, genetic interaction analysis shows that spir functionally interacts with Dorsocross, tin, and pannier to properly specify the cardiac fate...
2012: PloS One
https://www.readbyqxmd.com/read/22268758/probing-the-polygenic-basis-of-cardiomyopathies-in-drosophila
#15
REVIEW
Li Qian, Rolf Bodmer
In trying to understand the causes for congenital heart disease and cardiomyopathies, it is difficult to study polygenic interactions that contribute to the severity of the disease, which is in part due to genetic complexity and generation time of higher organisms that hinder efficient screening for modifiers of primary causes of heart disease. The adult Drosophila heart has recently been established as a model to probe genetic interactions that lead to cardiac dysfunction in this genetically simple and short-lived organism...
May 2012: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/22056672/nkx2-2-repressor-complex-regulates-islet-%C3%AE-cell-specification-and-prevents-%C3%AE-to-%C3%AE-cell-reprogramming
#16
James B Papizan, Ruth A Singer, Shuen-Ing Tschen, Sangeeta Dhawan, Jessica M Friel, Susan B Hipkens, Mark A Magnuson, Anil Bhushan, Lori Sussel
Regulation of cell differentiation programs requires complex interactions between transcriptional and epigenetic networks. Elucidating the principal molecular events responsible for the establishment and maintenance of cell fate identities will provide important insights into how cell lineages are specified and maintained and will improve our ability to recapitulate cell differentiation events in vitro. In this study, we demonstrate that Nkx2.2 is part of a large repression complex in pancreatic β cells that includes DNMT3a, Grg3, and HDAC1...
November 1, 2011: Genes & Development
https://www.readbyqxmd.com/read/21965617/jak-stat-signaling-regulates-heart-precursor-diversification-in-drosophila
#17
Aaron N Johnson, Mayssa H Mokalled, Tom N Haden, Eric N Olson
Intercellular signal transduction pathways regulate the NK-2 family of transcription factors in a conserved gene regulatory network that directs cardiogenesis in both flies and mammals. The Drosophila NK-2 protein Tinman (Tin) was recently shown to regulate Stat92E, the Janus kinase (JAK) and Signal transducer and activator of transcription (Stat) pathway effector, in the developing mesoderm. To understand whether the JAK/Stat pathway also regulates cardiogenesis, we performed a systematic characterization of JAK/Stat signaling during mesoderm development...
November 2011: Development
https://www.readbyqxmd.com/read/21901108/specification-of-drosophila-corpora-cardiaca-neuroendocrine-cells-from-mesoderm-is-regulated-by-notch-signaling
#18
Sangbin Park, Erika L Bustamante, Julie Antonova, Graeme W McLean, Seung K Kim
Drosophila neuroendocrine cells comprising the corpora cardiaca (CC) are essential for systemic glucose regulation and represent functional orthologues of vertebrate pancreatic α-cells. Although Drosophila CC cells have been regarded as developmental orthologues of pituitary gland, the genetic regulation of CC development is poorly understood. From a genetic screen, we identified multiple novel regulators of CC development, including Notch signaling factors. Our studies demonstrate that the disruption of Notch signaling can lead to the expansion of CC cells...
August 2011: PLoS Genetics
https://www.readbyqxmd.com/read/21690310/tinman-nkx2-5-acts-via-mir-1-and-upstream-of-cdc42-to-regulate-heart-function-across-species
#19
Li Qian, Joshua D Wythe, Jiandong Liu, Jerome Cartry, Georg Vogler, Bhagyalaxmi Mohapatra, Robyn T Otway, Yu Huang, Isabelle N King, Marjorie Maillet, Yi Zheng, Timothy Crawley, Ouarda Taghli-Lamallem, Christopher Semsarian, Sally Dunwoodie, David Winlaw, Richard P Harvey, Diane Fatkin, Jeffrey A Towbin, Jeffery D Molkentin, Deepak Srivastava, Karen Ocorr, Benoit G Bruneau, Rolf Bodmer
Unraveling the gene regulatory networks that govern development and function of the mammalian heart is critical for the rational design of therapeutic interventions in human heart disease. Using the Drosophila heart as a platform for identifying novel gene interactions leading to heart disease, we found that the Rho-GTPase Cdc42 cooperates with the cardiac transcription factor Tinman/Nkx2-5. Compound Cdc42, tinman heterozygous mutant flies exhibited impaired cardiac output and altered myofibrillar architecture, and adult heart-specific interference with Cdc42 function is sufficient to cause these same defects...
June 27, 2011: Journal of Cell Biology
https://www.readbyqxmd.com/read/21232234/heart-development-in-drosophila-and-its-relationship-to-vertebrates
#20
R Bodmer
The discovery of the vertebrate hox gene clusters and their structural and functional relationship to the Drosophila HOM-C cluster of homeotic genes revealed amazing similarities between the developmental mechanisms by which a major body axis is formed in vertebrates and those of many invertebrates, possibly encompassing all multicellular organisms. Recent data suggest that heart development in Drosophila also resembles vertebrate heart development in several fundamental aspects despite the drastic morphologic differences between them...
January 1995: Trends in Cardiovascular Medicine
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