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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
#1
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...
February 14, 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
#2
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
#3
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
#4
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
#5
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...
January 13, 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
#6
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
#7
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
https://www.readbyqxmd.com/read/27939581/expression-of-terminal-effector-genes-in-mammalian-neurons-is-maintained-by-a-dynamic-relay-of-transient-enhancers
#8
Ho Sung Rhee, Michael Closser, Yuchun Guo, Elizaveta V Bashkirova, G Christopher Tan, David K Gifford, Hynek Wichterle
Generic spinal motor neuron identity is established by cooperative binding of programming transcription factors (TFs), Isl1 and Lhx3, to motor-neuron-specific enhancers. How expression of effector genes is maintained following downregulation of programming TFs in maturing neurons remains unknown. High-resolution exonuclease (ChIP-exo) mapping revealed that the majority of enhancers established by programming TFs are rapidly deactivated following Lhx3 downregulation in stem-cell-derived hypaxial motor neurons...
December 21, 2016: Neuron
https://www.readbyqxmd.com/read/27939218/a-multi-step-transcriptional-and-chromatin-state-cascade-underlies-motor-neuron-programming-from-embryonic-stem-cells
#9
Silvia Velasco, Mahmoud M Ibrahim, Akshay Kakumanu, Görkem Garipler, Begüm Aydin, Mohamed Ahmed Al-Sayegh, Antje Hirsekorn, Farah Abdul-Rahman, Rahul Satija, Uwe Ohler, Shaun Mahony, Esteban O Mazzoni
Direct cell programming via overexpression of transcription factors (TFs) aims to control cell fate with the degree of precision needed for clinical applications. However, the regulatory steps involved in successful terminal cell fate programming remain obscure. We have investigated the underlying mechanisms by looking at gene expression, chromatin states, and TF binding during the uniquely efficient Ngn2, Isl1, and Lhx3 motor neuron programming pathway. Our analysis reveals a highly dynamic process in which Ngn2 and the Isl1/Lhx3 pair initially engage distinct regulatory regions...
February 2, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/27819291/isl1-based-lim-complexes-control-slit2-transcription-in-developing-cranial-motor-neurons
#10
Kyung-Tai Kim, Namhee Kim, Hwan-Ki Kim, Hojae Lee, Hannah N Gruner, Peter Gergics, Chungoo Park, Grant S Mastick, Hae-Chul Park, Mi-Ryoung Song
LIM-homeodomain (HD) transcription factors form a multimeric complex and assign neuronal subtype identities, as demonstrated by the hexameric ISL1-LHX3 complex which gives rise to somatic motor (SM) neurons. However, the roles of combinatorial LIM code in motor neuron diversification and their subsequent differentiation is much less well understood. In the present study, we demonstrate that the ISL1 controls postmitotic cranial branchiomotor (BM) neurons including the positioning of the cell bodies and peripheral axon pathfinding...
November 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27818139/cited2-cooperates-with-isl1-and-promotes-cardiac-differentiation-of-mouse-embryonic-stem-cells
#11
Ivette Pacheco-Leyva, Ana Catarina Matias, Daniel V Oliveira, João M A Santos, Rita Nascimento, Eduarda Guerreiro, Anna C Michell, Annebel M van De Vrugt, Gisela Machado-Oliveira, Guilherme Ferreira, Ibrahim Domian, José Bragança
The transcriptional regulator CITED2 is essential for heart development. Here, we investigated the role of CITED2 in the specification of cardiac cell fate from mouse embryonic stem cells (ESC). The overexpression of CITED2 in undifferentiated ESC was sufficient to promote cardiac cell emergence upon differentiation. Conversely, the depletion of Cited2 at the onset of differentiation resulted in a decline of ESC ability to generate cardiac cells. Moreover, loss of Cited2 expression impairs the expression of early mesoderm markers and cardiogenic transcription factors (Isl1, Gata4, Tbx5)...
December 13, 2016: Stem Cell Reports
https://www.readbyqxmd.com/read/27794491/vegf-regulates-relative-allocation-of-isl1-cardiac-progenitors-to-myocardial-and-endocardial-lineages
#12
Zhiheng He, Myriam Grunewald, Yuval Dor, Eli Keshet
A fundamental issue in organogenesis is how dichotomous fate decisions are made securing proper allocation of multipotent progenitors to their respective descendants. Previous lineage tracing analyses showing Isl1(+)/VEGFR2(+) cardiac progenitors in the second heart field give rise to both endocardium and myocardium suggest VEGF plays a role in this fate decision, conceivably promoting an endocardial fate. Isl1(+) multipotent progenitors and lineage-committed descendants thereof were visualized and quantified within their transition zone in the outflow tract...
November 2016: Mechanisms of Development
https://www.readbyqxmd.com/read/27672361/transgenic-gdnf-positively-influences-proliferation-differentiation-maturation-and-survival-of-motor-neurons-produced-from-mouse-embryonic-stem-cells
#13
Daniel Cortés, Yolanda Robledo-Arratia, Ricardo Hernández-Martínez, Itzel Escobedo-Ávila, José Bargas, Iván Velasco
Embryonic stem cells (ESC) are pluripotent and thus can differentiate into every cell type present in the body. Directed differentiation into motor neurons (MNs) has been described for pluripotent cells. Although neurotrophic factors promote neuronal survival, their role in neuronal commitment is elusive. Here, we developed double-transgenic lines of mouse ESC (mESC) that constitutively produce glial cell line-derived neurotrophic factor (GDNF) and also contain a GFP reporter, driven by HB9, which is expressed only by postmitotic MNs...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27659340/characterization-and-tissue-distribution-of-lhx9-and-lhx9%C3%AE-in-chinese-giant-salamander-andrias-davidianus
#14
Qiaomu Hu, Haifeng Tian, Yan Meng, Hanbing Xiao
Lhx9 is an LIM (named for the first three proteins in which the domain was found, Lin-11, Isl1 and Mec-3) homeodomain protein involved in development and differentiation of the gonad. In this study, we isolated the full-length Lhx9 and Lhx9α from Andrias davidianus, detected the tissue distribution and analysed the methylation of the promoters. We identified Lhx9 of 1411 bp and Lhx9α of 1153-bp length, differing in the 3'-flanking region, encoding 399 and 330 amino acids, respectively. The Lhx9 gene was detected primarily in liver, ovary and heart with moderate expression in brain, pituitary, intestine and spleen, and low expression in the remaining examined tissues, while Lhx9α expression was high in heart, pituitary and liver, and low in spleen and stomach...
September 2016: Journal of Genetics
https://www.readbyqxmd.com/read/27649475/epispadias-and-the-associated-embryopathies-genetic-and-developmental-basis
#15
REVIEW
K Suzuki, D Matsumaru, S Matsushita, A Murashima, M Ludwig, H Reutter, G Yamada
The abnormalities in the urogenital organs are frequently observed as human developmental diseases. Among such diseases, the defects in the upper part of external genitalia are rather rare named epispadias. The cleft in the dorsal part of external genitalia often reaches to the urethra. In general, the urogenital abnormalities accompany defects in the adjacent tissues and organs. The ventral body wall and bladder can also be affected in the patients with dorsal defects of the external genitalia. Therefore, such multiple malformations are often classified as bladder exstrophy and epispadias complex (BEEC)...
February 2017: Clinical Genetics
https://www.readbyqxmd.com/read/27578785/the-lim-homeobox-transcription-factor-isl1-plays-crucial-roles-in-the-development-of-multiple-arcuate-nucleus-neurons
#16
Bora Lee, Seunghee Lee, Soo-Kyung Lee, Jae W Lee
Neurons in the hypothalamic arcuate nucleus relay and translate important cues from the periphery into the central nervous system. However, the gene regulatory program directing their development remains poorly understood. Here, we report that the LIM-homeodomain transcription factor Isl1 is expressed in several subpopulations of developing arcuate neurons and plays crucial roles in their fate specification. Mice with conditional deletion of the Isl1 gene in developing hypothalamus display severe deficits in both feeding and linear growth...
October 15, 2016: Development
https://www.readbyqxmd.com/read/27532212/pou4f2-gfp-knock-in-mouse-line-a-model-for-studying-retinal-ganglion-cell-development
#17
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
https://www.readbyqxmd.com/read/27525311/isl1-cardiovascular-progenitor-cells-for-cardiac-repair-after-myocardial-infarction
#18
Oscar Bartulos, Zhen Wu Zhuang, Yan Huang, Nicole Mikush, Carol Suh, Alda Bregasi, Lin Wang, William Chang, Diane S Krause, Lawrence H Young, Jordan S Pober, Yibing Qyang
Cardiovascular progenitor cells (CPCs) expressing the ISL1-LIM-homeodomain transcription factor contribute developmentally to cardiomyocytes in all 4 chambers of the heart. Here, we show that ISL1-CPCs can be applied to myocardial regeneration following injury. We used a rapid 3D methylcellulose approach to form murine and human ISL1-CPC spheroids that engrafted after myocardial infarction in murine hearts, where they differentiated into cardiomyocytes and endothelial cells, integrating into the myocardium and forming new blood vessels...
July 7, 2016: JCI Insight
https://www.readbyqxmd.com/read/27485686/neuronal-deletion-of-kmt2a-mll1-histone-methyltransferase-in-ventral-striatum-is-associated-with-defective-spike-timing-dependent-striatal-synaptic-plasticity-altered-response-to-dopaminergic-drugs-and-increased-anxiety
#19
Erica Y Shen, Yan Jiang, Behnam Javidfar, Bibi Kassim, Yong-Hwee E Loh, Qi Ma, Amanda C Mitchell, Venu Pothula, A Francis Stewart, Patricia Ernst, Wei-Dong Yao, Gilles Martin, Li Shen, Mira Jakovcevski, Schahram Akbarian
Lysine (K) methyltransferase 2a (Kmt2a) and other regulators of H3 lysine 4 methylation, a histone modification enriched at promoters and enhancers, are widely expressed throughout the brain, but molecular and cellular phenotypes in subcortical areas remain poorly explored. We report that Kmt2a conditional deletion in postnatal forebrain is associated with excessive nocturnal activity and with absent or blunted responses to stimulant and dopaminergic agonist drugs, in conjunction with near-complete loss of spike-timing-dependent long-term potentiation in medium spiny neurons (MSNs)...
December 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27446404/early-detection-of-tumor-relapse-regrowth-by-consecutive-minimal-residual-disease-monitoring-in-high-risk-neuroblastoma-patients
#20
Satoshi Hirase, Atsuro Saitoh, Tri Budi Hartomo, Aiko Kozaki, Tomoko Yanai, Daiichiro Hasegawa, Keiichiro Kawasaki, Yoshiyuki Kosaka, Masafumi Matsuo, Nobuyuki Yamamoto, Takeshi Mori, Akira Hayakawa, Kazumoto Iijima, Hisahide Nishio, Noriyuki Nishimura
Neuroblastoma is an aggressive pediatric tumor accounting for ~15% of cancer-associated mortalities in children. Despite the current intensive therapy, >50% of high-risk patients experience tumor relapse or regrowth caused by the activation of minimal residual disease (MRD). Although several MRD detection protocols using various reverse transcription-quantitative polymerase chain reaction (RT-qPCR) markers have been reported to evaluate the therapeutic response and disease status of neuroblastoma patients, their clinical significance remains elusive...
August 2016: Oncology Letters
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