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https://www.readbyqxmd.com/read/28676648/interactions-between-lhx3-and-isl1-family-lim-homeodomain-transcription-factors-are-conserved-in-caenorhabditis-elegans
#1
Mugdha Bhati, Estelle Llamosas, David A Jacques, Cy M Jeffries, Siavoush Dastmalchi, Nina Ripin, Hannah R Nicholas, Jacqueline M Matthews
LIM-Homeodomain (LIM-HD) transcription factors are highly conserved in animals where they are thought to act in a transcriptional 'LIM code' that specifies cell types, particularly in the central nervous system. In chick and mammals the interaction between two LIM-HD proteins, LHX3 and Islet1 (ISL1), is essential for the development of motor neurons. Using yeast two-hybrid analysis we showed that the Caenorhabditis elegans orthologs of LHX3 and ISL1, CEH-14 and LIM-7 can physically interact. Structural characterisation of a complex comprising the LIM domains from CEH-14 and a LIM-interaction domain from LIM-7 showed that these nematode proteins assemble to form a structure that closely resembles that of their vertebrate counterparts...
July 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28671548/motoneurons-regulate-the-central-pattern-generator-during-drug-induced-locomotor-like-activity-in-the-neonatal-mouse
#2
Melanie Falgairolle, Joshua G Puhl, Avinash Pujala, Wenfang Liu, Michael James O'Donovan
Motoneurons are traditionally viewed as the output of the spinal cord that do not influence locomotor rhythmogenesis. We assessed the role of motoneuron firing during ongoing locomotor-like activity in neonatal mice expressing archaerhopsin-3 (Arch), halorhodopsin (eNpHR), or channelrhodopsin-2 (ChR2) in Choline acetyltransferase expressing neurons (ChAT(+)) or the LIM-homeodomain transcription factor Isl1(+) neurons. Illumination of the lumbar cord in mice expressing eNpHR or Arch in ChAT(+) or Isl1(+) neurons, depressed motoneuron discharge, transiently decreased the frequency, and perturbed the phasing of the locomotor-like rhythm...
July 3, 2017: ELife
https://www.readbyqxmd.com/read/28650075/isl1-controls-patterning-and-mineralization-of-enamel-in-the-continuously-renewing-mouse-incisor
#3
Adrien Naveau, Bin Zhang, Bo Meng, McGarrett T Sutherland, Michaela Prochazkova, Timothy Wen, Pauline Marangoni, Kyle B Jones, Timothy C Cox, Bernhard Ganss, Andrew H Jheon, Ophir D Klein
Rodents are characterized by continuously renewing incisors whose growth is fueled by epithelial and mesenchymal stem cells housed in the proximal compartments of the tooth. The epithelial stem cells reside in structures known as the labial (toward the lip) and lingual (toward the tongue) cervical loops (laCL and liCL, respectively). An important feature of the rodent incisor is that enamel, the outer, highly mineralized layer, is asymmetrically distributed, as it is normally generated by the laCL but not the liCL...
June 26, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28648899/transient-hes5-activity-instructs-mesodermal-cells-toward-a-cardiac-fate
#4
Ana G Freire, Avinash Waghray, Francisca Soares-da-Silva, Tatiana P Resende, Dung-Fang Lee, Carlos-Filipe Pereira, Diana S Nascimento, Ihor R Lemischka, Perpétua Pinto-do-Ó
Notch signaling plays a role in specifying a cardiac fate but the downstream effectors remain unknown. In this study we implicate the Notch downstream effector HES5 in cardiogenesis. We show transient Hes5 expression in early mesoderm of gastrulating embryos and demonstrate, by loss and gain-of-function experiments in mouse embryonic stem cells, that HES5 favors cardiac over primitive erythroid fate. Hes5 overexpression promotes upregulation of the cardiac gene Isl1, while the hematopoietic regulator Scl is downregulated...
July 11, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28647274/sonic-hedgehog-pathway-suppression-and-reactivation-accelerates-differentiation-of-rat-adipose-derived-mesenchymal-stromal-cells-toward-insulin-producing-cells
#5
Dian Dayer, Mahmoud Hashemi Tabar, Eskandar Moghimipour, Mohammad Reza Tabandeh, Ata A Ghadiri, Elham Allah Bakhshi, Mahmoud Orazizadeh, Mohammad Ali Ghafari
BACKGROUND AIMS: Sonic hedgehog (Shh) is an intercellular signaling molecule that regulates pancreas development in mammals. Manipulation of Shh signaling pathway can be used as reliable approach to improve the generation of functional insulin-producing cells (IPCs) from mesenchymal stromal cells (MSCs). METHODS: In the present study, a novel differentiation protocol was used to produce IPCs from adipose tissue-derived MSCs (ATDMSCs) based on sequential inhibition and reactivation of Shh pathway...
June 21, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28624850/the-plant-lim-proteins-unlocking-the-hidden-attractions
#6
REVIEW
Vikas Srivastava, Praveen Kumar Verma
The plant LIMs comprise two sub-families with one (DA1/DAR) and two (2LIM) LIM domains. This review comprehensively discussed the structure and potential role of this protein family in diverse area of plant biology. The description of first eukaryote lineage-specific plant LIM domain (LIN11, ISL1, and MEC3) proteins was observed in Helianthus long back. The successive study of LIM proteins in diverse plants has shown its vital relation to development, metabolism and defence. This nascent gene family has been worked out for their role in actin dynamics, organ size determination and transcription regulation...
June 17, 2017: Planta
https://www.readbyqxmd.com/read/28586118/a-dna-hypermethylation-profile-reveals-new-potential-biomarkers-for-the-evaluation-of-prognosis-in-urothelial-bladder-cancer
#7
Jose I López, Javier C Angulo, Ana Martín, Manuel Sánchez-Chapado, Ana González-Corpas, Begoña Colás, Santiago Ropero
DNA hypermethylation has emerged as a molecular biomarker for the evaluation of cancer diagnosis and prognosis. We define a methylation signature of bladder cancer and evaluate whether this profile assesses prognosis of patients. Genome-wide methylation analysis was performed on 70 tumor and 10 normal bladder samples. Hypermethylation status of 1505 CpGs present in the promoter region of 807 genes was studied. Thirty-three genes were significantly hypermethylated in ≥10% of the tumors. Three clusters of patients were characterized by their DNA methylation profile, one at higher risk of dead of disease (p = 0...
June 6, 2017: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
https://www.readbyqxmd.com/read/28498280/immunohistochemical-characterization-of-the-origins-of-metastatic-well-differentiated-neuroendocrine-tumors-to-the-liver
#8
Zhaohai Yang, David S Klimstra, Ralph H Hruban, Laura H Tang
Metastatic neoplasms of unknown primary site pose a major challenge to patient management. As targeted therapies are now being tailored to neuroendocrine tumors (NETs) of different primary sites, identifying the origin of metastatic NETs has become increasingly important. Compared with more extensive efforts on metastatic adenocarcinomas of unknown primary, the literature on metastatic NETs (often to the liver) is relatively sparse and most studies are based on primary tumors. We sought to study metastatic well-differentiated NETs to the liver to identify markers that predict the site of origin...
July 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28472858/selective-neuronal-expression-of-the-soxe-factor-sox8-in-direct-pathway-striatal-projection-neurons-of-the-developing-mouse-brain
#9
Paloma Merchan-Sala, Diana Nardini, Ronald R Waclaw, Kenneth Campbell
The striatum is the major component of the basal ganglia and is well known to play a key role in the control of motor function via balanced output from the indirect (iSPNs) and direct pathway striatal projection neurons (dSPNs). Little is known, however, about the molecular genetic mechanisms that control the formation of the iSPNs versus dSPNs. We show here that the SoxE family member, Sox8, is co-expressed with the dSPN markers, Isl1 and Ebf1, in the developing striatum. Moreover, dSPNs, as marked by Isl1-cre fate map, express Sox8 in the embryonic striatum and Sox8-EGFP BAC transgenic mice specifically reveal the direct pathway axons during development...
May 4, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28451636/the-isl1-lhx3-complex-promotes-motor-neuron-specification-by-activating-transcriptional-pathways-that-enhance-its-own-expression-and-formation
#10
Madalynn Erb, Bora Lee, So Yeon Seo, Jae W Lee, Seunghee Lee, Soo-Kyung Lee
Motor neuron (MN) progenitor cells rapidly induce high expression of the transcription factors Islet-1 (Isl1), LIM-homeobox 3 (Lhx3), and the transcriptional regulator LMO4, as they differentiate. While these factors are critical for MN specification, the mechanisms regulating their precise temporal and spatial expression patterns are not well characterized. Isl1 and Lhx3 form the Isl1-Lhx3 complex, which induces the transcription of genes critical for MN specification and maturation. Here, we report that Isl1, Lhx3, and Lmo4 are direct target genes of the Isl1-Lhx3 complex...
March 2017: ENeuro
https://www.readbyqxmd.com/read/28436940/disruption-of-spatiotemporal-hypoxic-signaling-causes-congenital-heart-disease-in-mice
#11
Xuejun Yuan, Hui Qi, Xiang Li, Fan Wu, Jian Fang, Eva Bober, Gergana Dobreva, Yonggang Zhou, Thomas Braun
Congenital heart disease (CHD) represents the most prevalent inborn anomaly. Only a minority of CHD cases are attributed to genetic causes, suggesting a major role of environmental factors. Nonphysiological hypoxia during early pregnancy induces CHD, but the underlying reasons are unknown. Here, we have demonstrated that cells in the mouse heart tube are hypoxic, while cardiac progenitor cells (CPCs) expressing islet 1 (ISL1) in the secondary heart field (SHF) are normoxic. In ISL1+ CPCs, induction of hypoxic responses caused CHD by repressing Isl1 and activating NK2 homeobox 5 (Nkx2...
June 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28386378/transplantation-of-multipotent-isl1-cardiac-progenitor-cells-preserves-infarcted-heart-function-in-mice
#12
Yunpeng Li, Shuo Tian, Ienglam Lei, Liu Liu, Peter Ma, Zhong Wang
Cell-based cardiac therapy is a promising therapeutic strategy to restore heart function after myocardial infarction (MI). However, the cell type selection and ensuing effects remain controversial. Here, we intramyocardially injected Isl1+ cardiac progenitor cells (CPCs) derived from EGFP/luciferase double-tagged mouse embryonic stem (dt-mES) cells with vehicle (fibrin gel) or phosphate-buffered saline (PBS) into the infarcted area in nude mice to assess the contribution of CPCs to the recovery of cardiac function post-MI...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28257739/candidate-gene-analyses-of-3-dimensional-dentoalveolar-phenotypes-in-subjects-with-malocclusion
#13
Cole A Weaver, Steven F Miller, Clarissa S G da Fontoura, George L Wehby, Brad A Amendt, Nathan E Holton, Veeratrishul Allareddy, Thomas E Southard, Lina M Moreno Uribe
INTRODUCTION: Genetic studies of malocclusion etiology have identified 4 deleterious mutations in genes DUSP6,ARHGAP21, FGF23, and ADAMTS1 in familial Class III cases. Although these variants may have large impacts on Class III phenotypic expression, their low frequency (<1%) makes them unlikely to explain most malocclusions. Thus, much of the genetic variation underlying the dentofacial phenotypic variation associated with malocclusion remains unknown. In this study, we evaluated associations between common genetic variations in craniofacial candidate genes and 3-dimensional dentoalveolar phenotypes in patients with malocclusion...
March 2017: American Journal of Orthodontics and Dentofacial Orthopedics
https://www.readbyqxmd.com/read/28213137/foxo1-is-a-downstream-effector-of-isl1-in-direct-pathway-striatal-projection-neuron-development-within-the-embryonic-mouse-telencephalon
#14
R R Waclaw, L A Ehrman, P Merchan-Sala, V Kohli, D Nardini, K Campbell
Recent studies have shown that the LIM-homeodomain transcription factor Isl1 is required for the survival and differentiation of direct pathway striatonigral neurons during embryonic development. The downstream effectors of Isl1 in these processes are presently unknown. We show here that Foxo1, a transcription factor that has been implicated in cell survival, is expressed in striatal projection neurons (SPNs) that derive from the Isl1 lineage (i.e. direct pathway SPNs). Moreover, Isl1 conditional knockouts (cKOs) show a severe loss of Foxo1 expression at E15...
April 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28176844/isl1-is-a-major-susceptibility-gene-for-classic-bladder-exstrophy-and-a-regulator-of-urinary-tract-development
#15
Rong Zhang, Michael Knapp, Kentaro Suzuki, Daiki Kajioka, Johanna M Schmidt, Jonas Winkler, Öznur Yilmaz, Michael Pleschka, Jia Cao, Christina Clementson Kockum, Gillian Barker, Gundela Holmdahl, Glenda Beaman, David Keene, Adrian S Woolf, Raimondo M Cervellione, Wei Cheng, Simon Wilkins, John P Gearhart, Fabio Sirchia, Massimo Di Grazia, Anne-Karolin Ebert, Wolfgang Rösch, Jörg Ellinger, Ekkehart Jenetzky, Nadine Zwink, Wout F Feitz, Carlo Marcelis, Johannes Schumacher, Federico Martinón-Torres, Martin Lloyd Hibberd, Chiea Chuen Khor, Stefanie Heilmann-Heimbach, Sandra Barth, Simeon A Boyadjiev, Alfredo Brusco, Michael Ludwig, William Newman, Agneta Nordenskjöld, Gen Yamada, Benjamin Odermatt, Heiko Reutter
Previously genome-wide association methods in patients with classic bladder exstrophy (CBE) found association with ISL1, a master control gene expressed in pericloacal mesenchyme. This study sought to further explore the genetics in a larger set of patients following-up on the most promising genomic regions previously reported. Genotypes of 12 markers obtained from 268 CBE patients of Australian, British, German Italian, Spanish and Swedish origin and 1,354 ethnically matched controls and from 92 CBE case-parent trios from North America were analysed...
February 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28139974/the-lim-protein-complex-establishes-a-retinal-circuitry-of-visual-adaptation-by-regulating-pax6-%C3%AE-enhancer-activity
#16
Yeha Kim, Soyeon Lim, Taejeong Ha, You-Hyang Song, Young-In Sohn, Dae-Jin Park, Sun-Sook Paik, Joo-Ri Kim-Kaneyama, Mi-Ryoung Song, Amanda Leung, Edward M Levine, In-Beom Kim, Yong Sook Goo, Seung-Hee Lee, Kyung Hwa Kang, Jin Woo Kim
The visual responses of vertebrates are sensitive to the overall composition of retinal interneurons including amacrine cells, which tune the activity of the retinal circuitry. The expression of Paired-homeobox 6 (PAX6) is regulated by multiple cis-DNA elements including the intronic α-enhancer, which is active in GABAergic amacrine cell subsets. Here, we report that the transforming growth factor ß1-induced transcript 1 protein (Tgfb1i1) interacts with the LIM domain transcription factors Lhx3 and Isl1 to inhibit the α-enhancer in the post-natal mouse retina...
January 31, 2017: ELife
https://www.readbyqxmd.com/read/28106108/isl2b-regulates-anterior-second-heart-field-development-in-zebrafish
#17
Hagen R Witzel, Sirisha Cheedipudi, Rui Gao, Didier Y R Stainier, Gergana D Dobreva
After initial formation, the heart tube grows by addition of second heart field progenitor cells to its poles. The transcription factor Isl1 is expressed in the entire second heart field in mouse, and Isl1-deficient mouse embryos show defects in arterial and venous pole development. The expression of Isl1 is conserved in zebrafish cardiac progenitors; however, Isl1 is required for cardiomyocyte differentiation only at the venous pole. Here we show that Isl1 homologues are expressed in specific patterns in the developing zebrafish heart and play distinct roles during cardiac morphogenesis...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28099929/modeling-the-phenotype-of-spinal-muscular-atrophy-by-the-direct-conversion-of-human-fibroblasts-to-motor-neurons
#18
Qi-Jie Zhang, Jin-Jing Li, Xiang Lin, Ying-Qian Lu, Xin-Xin Guo, En-Lin Dong, Miao Zhao, Jin He, Ning Wang, Wan-Jin Chen
Spinal muscular atrophy (SMA) is a lethal autosomal recessive neurological disease characterized by selective degeneration of motor neurons in the spinal cord. In recent years, the development of cellular reprogramming technology has provided an alternative and effective method for obtaining patient-specific neurons in vitro. In the present study, we applied this technology to the field of SMA to acquire patient-specific induced motor neurons that were directly converted from fibroblasts via the forced expression of 8 defined transcription factors...
February 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28000708/protein-inhibitor-of-activated-stat-y-piasy-regulates-insulin-secretion-by-interacting-with-lim-homeodomain-transcription-factor-isl1
#19
Chengzhi Yan, Chulin Yu, Di Zhang, Yan Cui, Jinlian Zhou, Sheng Cui
It is known that the LIM homeodomain transcription factor Isl1 is highly expressed in all pancreatic endocrine cells and functions in regulating pancreatic development and insulin secretion. The Isl1 mutation has been found to be associated with type 2 diabetes, but the mechanism responsible for Isl1 regulation of insulin synthesis and secretion still needs to be elucidated. In the present study, the protein inhibitor of activated STAT Y (PIASy) was identified as a novel Isl1-interacting protein with a yeast two-hybrid system, and its interaction with Isl1 was further confirmed by a co-immunoprecipitation experiment...
December 21, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27941246/lim-domain-binding-1-maintains-the-terminally-differentiated-state-of-pancreatic-%C3%AE-cells
#20
Benjamin N Ediger, Hee-Woong Lim, Christine Juliana, David N Groff, LaQueena T Williams, Giselle Dominguez, Jin-Hua Liu, Brandon L Taylor, Erik R Walp, Vasumathi Kameswaran, Juxiang Yang, Chengyang Liu, Chad S Hunter, Klaus H Kaestner, Ali Naji, Changhong Li, Maike Sander, Roland Stein, Lori Sussel, Kyoung-Jae Won, Catherine Lee May, Doris A Stoffers
The recognition of β cell dedifferentiation in type 2 diabetes raises the translational relevance of mechanisms that direct and maintain β cell identity. LIM domain-binding protein 1 (LDB1) nucleates multimeric transcriptional complexes and establishes promoter-enhancer looping, thereby directing fate assignment and maturation of progenitor populations. Many terminally differentiated endocrine cell types, however, remain enriched for LDB1, but its role is unknown. Here, we have demonstrated a requirement for LDB1 in maintaining the terminally differentiated status of pancreatic β cells...
January 3, 2017: Journal of Clinical Investigation
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