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https://www.readbyqxmd.com/read/29139167/the-zinc-finger-gene-nolz1-regulates-the-formation-of-retinal-progenitor-cells-and-suppresses-the-lim3-lhx3-phenotype-of-retinal-bipolar-cells-in-chicken-retina
#1
Maria K E Blixt, Dardan Konjusha, Henrik Ring, Finn Hallböök
BACKGROUND: The zinc-finger transcription factor Nolz1 regulates spinal cord neuron development by interacting with the transcription factors Isl1, Lim1 and Lim3, which are also important for photoreceptors, horizontal and bipolar cells during retinal development. We therefore studied Nolz1 during retinal development. RESULTS: Nolz1 expression was seen in two waves during development: one early (peak at embryonic day 3-4.5) in retinal progenitors and one late (embryonic day 8) in newly differentiated cells in the inner nuclear layer...
November 15, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/29065928/chromatin-status-and-transcription-factor-binding-to-gonadotropin-promoters-in-gonadotrope-cell-lines
#2
Huimin Xie, Hanne M Hoffmann, Anita K Iyer, Melissa J Brayman, Cindy Ngo, Mary Jean Sunshine, Pamela L Mellon
BACKGROUND: Proper expression of key reproductive hormones from gonadotrope cells of the pituitary is required for pubertal onset and reproduction. To further our understanding of the molecular events taking place during embryonic development, leading to expression of the glycoproteins luteinizing hormone (LH) and follicle-stimulating hormone (FSH), we characterized chromatin structure changes, imparted mainly by histone modifications, in model gonadotrope cell lines. METHODS: We evaluated chromatin status and gene expression profiles by chromatin immunoprecipitation assays, DNase sensitivity assay, and RNA sequencing in three developmentally staged gonadotrope cell lines, αT1-1 (progenitor, expressing Cga), αT3-1 (immature, expressing Cga and Gnrhr), and LβT2 (mature, expressing Cga, Gnrhr, Lhb, and Fshb), to assess changes in chromatin status and transcription factor access of gonadotrope-specific genes...
October 24, 2017: Reproductive Biology and Endocrinology: RB&E
https://www.readbyqxmd.com/read/28892058/glia-specific-enhancers-and-chromatin-structure-regulate-nfia-expression-and-glioma-tumorigenesis
#3
Stacey M Glasgow, Jeffrey C Carlson, Wenyi Zhu, Lesley S Chaboub, Peng Kang, Hyun Kyoung Lee, Yoanne M Clovis, Brittney E Lozzi, Robert J McEvilly, Michael G Rosenfeld, Chad J Creighton, Soo-Kyung Lee, Carrie A Mohila, Benjamin Deneen
Long-range enhancer interactions critically regulate gene expression, yet little is known about how their coordinated activities contribute to CNS development or how this may, in turn, relate to disease states. By examining the regulation of the transcription factor NFIA in the developing spinal cord, we identified long-range enhancers that recapitulate NFIA expression across glial and neuronal lineages in vivo. Complementary genetic studies found that Sox9-Brn2 and Isl1-Lhx3 regulate enhancer activity and NFIA expression in glial and neuronal populations...
November 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28886366/micrornas-induce-a-permissive-chromatin-environment-that-enables-neuronal-subtype-specific-reprogramming-of-adult-human-fibroblasts
#4
Daniel G Abernathy, Woo Kyung Kim, Matthew J McCoy, Allison M Lake, Rebecca Ouwenga, Seong Won Lee, Xiaoyun Xing, Daofeng Li, Hyung Joo Lee, Robert O Heuckeroth, Joseph D Dougherty, Ting Wang, Andrew S Yoo
Directed reprogramming of human fibroblasts into fully differentiated neurons requires massive changes in epigenetic and transcriptional states. Induction of a chromatin environment permissive for acquiring neuronal subtype identity is therefore a major barrier to fate conversion. Here we show that the brain-enriched miRNAs miR-9/9∗ and miR-124 (miR-9/9∗-124) trigger reconfiguration of chromatin accessibility, DNA methylation, and mRNA expression to induce a default neuronal state. miR-9/9∗-124-induced neurons (miNs) are functionally excitable and uncommitted toward specific subtypes but possess open chromatin at neuronal subtype-specific loci, suggesting that such identity can be imparted by additional lineage-specific transcription factors...
September 7, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28830788/zearalenone-and-alpha-zearalenol-inhibit-the-synthesis-and-secretion-of-pig-follicle-stimulating-hormone-via-the-non-classical-estrogen-membrane-receptor-gpr30
#5
Jing He, Chao Wei, Yueqin Li, Ying Liu, Yue Wang, Jirong Pan, Jiali Liu, Yingjie Wu, Sheng Cui
Zearalenone (ZEA) is one of the most popular endocrine-disrupting chemicals and is mainly produced by fungi of the genus Fusarium. The excessive intake of ZEA severely disrupts human and animal fertility by affecting the reproductive axis. However, most studies on the effects of ZEA and its metabolite α-zearalenol (α-ZOL) on reproductive systems have focused on gonads. Few studies have investigated the endocrine-disrupting effects of ZEA and α-ZOL on pituitary gonadotropins, including follicle-stimulating hormone (FSH) and luteinizing hormone (LH)...
August 19, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28807898/hypothalamic-sonic-hedgehog-is-required-for-cell-specification-and-proliferation-of-lhx3-lhx4-pituitary-embryonic-precursors
#6
Gabriela Carreno, John R Apps, Emily J Lodge, Leonidas Panousopoulos, Scott Haston, Jose Mario Gonzalez-Meljem, Heidi Hahn, Cynthia L Andoniadou, Juan Pedro Martinez-Barbera
Sonic hedgehog (SHH) is an essential morphogenetic signal that dictates cell fate decisions in several developing organs in mammals. In vitro data suggest that SHH is required to specify LHX3(+)/LHX4(+) Rathke's pouch (RP) progenitor identity. However, in vivo studies have failed to reveal such a function, supporting instead a crucial role for SHH in promoting proliferation of these RP progenitors and for differentiation of pituitary cell types. Here, we have used a genetic approach to demonstrate that activation of the SHH pathway is necessary to induce LHX3(+)/LHX4(+) RP identity in mouse embryos...
September 15, 2017: Development
https://www.readbyqxmd.com/read/28734020/molecular-analysis-of-brazilian-patients-with-combined-pituitary-hormone-deficiency-and-orthotopic-posterior-pituitary-lobe-reveals-eight-different-prop1-alterations-with-three-novel-mutations
#7
Joao Lo Madeira, Mirian Y Nishi, Marilena Nakaguma, Anna F Benedetti, Isabela Peixoto Biscotto, Thamiris Fernandes, Thiago Pequeno, Thalita Figueiredo, Marcela M Franca, Fernanda A Correa, Aline P Otto, Milena Abrão, Mirta B Miras, Silvana Santos, Alexander Al Jorge, Everlayny F Costalonga, Berenice B Mendonca, Ivo Jp Arnhold, Luciani R Carvalho
BACKGROUND: Mutations in PROP1, HESX1 and LHX3 are associated with combined pituitary hormone deficiency (CPHD) and orthotopic posterior pituitary lobe (OPP). OBJECTIVE: To identify mutations in PROP1, HESX1 and LHX3 in a large cohort of patients with CPHD and OPP (35 Brazilian, two Argentinian). DESIGN AND METHODS: We studied 23 index patients with CPHD and OPP (six familial and 17 sporadic) as well as 14 relatives. PROP1 was sequenced by the Sanger method in all except one sporadic case studied using a candidate gene panel...
July 22, 2017: Clinical Endocrinology
https://www.readbyqxmd.com/read/28731174/lhx3-is-an-early-stage-and-radiosensitivity-prognostic-biomarker-in-lung-adenocarcinoma
#8
Xin Lin, Yan Li, Jin Wang, Fei Han, Shuang Lu, Yu Wang, Wenjian Luo, Mingqian Zhang
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. We previously identified LHX3 as a new preferentially expressed gene in NSCLC. In the present study, we sought to determine its expression, the clinical relevance and the functional roles in NSCLC. LHX3 expression is sharply increased in carcinoma tissues compared to non-carcinoma tissues. Relational analysis reveals a significant association between LHX3 expression and clinical stage (n=172, p=0.032) or radiotherapy (n=167, p=0.022) of patients...
September 2017: Oncology Reports
https://www.readbyqxmd.com/read/28676648/interactions-between-lhx3-and-isl1-family-lim-homeodomain-transcription-factors-are-conserved-in-caenorhabditis-elegans
#9
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/28525353/molecular-genetics-of-growth-hormone-deficient-children-correlation-with-auxology-and-response-to-first-year-of-growth-hormone-therapy
#10
Vaman Khadilkar, Nikhil Phadke, Kavita Khatod, Veena Ekbote, Supriya Phanse Gupte, Ruchi Nadar, Anuradha Khadilkar
BACKGROUND: With the paucity of available literature correlating genetic mutation and response to treatment, we aimed to study the genetic makeup of children with growth hormone (GH) deficiency in Western India and correlate the mutation with auxology and response to GH treatment at end of 1 year. METHODS: Fifty-three (31 boys and 22 girls) children with severe short stature (height for age z-score <-3) and failed GH stimulation test were studied. Those having concomitant thyroid hormone or cortisol deficiencies were appropriately replaced prior to starting GH treatment...
May 24, 2017: Journal of Pediatric Endocrinology & Metabolism: JPEM
https://www.readbyqxmd.com/read/28476222/pituitary-hypoplasia
#11
REVIEW
Mariam Gangat, Sally Radovick
This article summarizes pituitary development and function as well as specific mutations of genes encoding the following transcription factors: HESX1, LHX3, LHX4, POU1F1, PROP1, and OTX2. Although several additional genetic defects related to hypopituitarism have been identified, this article focuses on these selected factors, as they have been well described in the literature in terms of clinical characterization of affected patients and molecular mechanisms of action, and therefore, are very relevant to clinical practice...
June 2017: Endocrinology and Metabolism Clinics of North America
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
#12
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/28356564/combined-pituitary-hormone-deficiency-due-to-gross-deletions-in-the-pou1f1-pit-1-and-prop1-genes
#13
Eleonore Bertko, Jürgen Klammt, Petra Dusatkova, Mithat Bahceci, Nazli Gonc, Louise Ten Have, Nurgun Kandemir, Georg Mansmann, Barbora Obermannova, Wilma Oostdijk, Heike Pfäffle, Denise Rockstroh-Lippold, Marina Schlicke, Alpaslan Kemal Tuzcu, Roland Pfäffle
Pituitary development depends on a complex cascade of interacting transcription factors and signaling molecules. Lesions in this cascade lead to isolated or combined pituitary hormone deficiency (CPHD). The aim of this study was to identify copy number variants (CNVs) in genes known to cause CPHD and to determine their structure. We analyzed 70 CPHD patients from 64 families. Deletions were found in three Turkish families and one family from northern Iraq. In one family we identified a 4.96 kb deletion that comprises the first two exons of POU1F1...
August 2017: Journal of Human Genetics
https://www.readbyqxmd.com/read/28332357/rare-frequency-of-mutations-in-pituitary-transcription-factor-genes-in-combined-pituitary-hormone-or-isolated-growth-hormone-deficiencies-in-korea
#14
Jin Ho Choi, Chang Woo Jung, Eungu Kang, Yoon Myung Kim, Sun Hee Heo, Beom Hee Lee, Gu Hwan Kim, Han Wook Yoo
PURPOSE: Congenital hypopituitarism is caused by mutations in pituitary transcription factors involved in the development of the hypothalamic-pituitary axis. Mutation frequencies of genes involved in congenital hypopituitarism are extremely low and vary substantially between ethnicities. This study was undertaken to compare the clinical, endocrinological, and radiological features of patients with an isolated growth hormone deficiency (IGHD) or combined pituitary hormone deficiency (CPHD)...
May 2017: Yonsei Medical Journal
https://www.readbyqxmd.com/read/28302169/two-novel-lhx3-mutations-in-patients-with-combined-pituitary-hormone-deficiency-including-cervical-rigidity-and-sensorineural-hearing-loss
#15
Khushnooda Ramzan, Bassam Bin-Abbas, Lolwa Al-Jomaa, Rabab Allam, Mohammed Al-Owain, Faiqa Imtiaz
BACKGROUND: Congenital combined pituitary hormone deficiency (CPHD) is a rare heterogeneous group of conditions. CPHD-type 3 (CPHD3; MIM# 221750) is caused by recessive mutations in LHX3, a LIM-homeodomain transcription factor gene. The isoforms of LHX3 are critical for pituitary gland formation and specification of the anterior pituitary hormone-secreting cell types. They also play distinct roles in the development of neuroendocrine and auditory systems. CASE PRESENTATION: Here, we summarize the clinical, endocrinological, radiological and molecular features of three patients from two unrelated families...
March 16, 2017: BMC Endocrine Disorders
https://www.readbyqxmd.com/read/28289583/microarray-technology-reveals-potentially-novel-genes-and-pathways-involved-in-non-functioning-pituitary-adenomas
#16
X Qiao, H Wang, X Wang, B Zhao, J Liu
Microarray data of non-functioning pituitary adenomas (NFPAs) were analyzed to disclose novel genes and pathways involved in NFPA tumorigenesis. Raw microarray data were downloaded from Gene Expression Omnibus. Data pre-treatment and differential analysis were conducted using packages in R. Functional and pathway enrichment analyses were performed using package GOs-tats. A protein-protein interaction (PPI) network was constructed using server STRING and Cytoscape. Known genes involved in pituitary adenomas (PAs), were obtained from the Comparative Toxicogenomics Database...
December 1, 2016: Balkan Journal of Medical Genetics: BJMG
https://www.readbyqxmd.com/read/28251550/the-mystery-of-puberty-initiation-genetics-and-epigenetics-of-idiopathic-central-precocious-puberty-icpp
#17
REVIEW
Sofia Leka-Emiri, George P Chrousos, Christina Kanaka-Gantenbein
Puberty is a major developmental stage. Damaging mutations, considered as "mistakes of nature", have contributed to the unraveling of the networks implicated in the normal initiation of puberty. Genes involved in the abnormal hypothalamic-pituitary-gonadal (HPG) axis development, in the normosmic idiopathic hypogonadotropic hypogonadism (nIHH), in the X-linked or autosomal forms of Kallmann syndrome and in precocious puberty have been identified (GNRH1, GNRHR, KISS1, GPR54, FGFR1, FGF8, PROK2, PROKR2, TAC3, TACR3, KAL1, PROK2, PROKR2, CHD7, LEP, LEPR, PC1, DAX1, SF-1, HESX-1, LHX3, PROP-1)...
August 2017: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/28139974/the-lim-protein-complex-establishes-a-retinal-circuitry-of-visual-adaptation-by-regulating-pax6-%C3%AE-enhancer-activity
#18
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/28127622/differential-methylation-of-genes-in-individuals-exposed-to-maternal-diabetes-in-utero
#19
Peng Chen, Paolo Piaggi, Michael Traurig, Clifton Bogardus, William C Knowler, Leslie J Baier, Robert L Hanson
AIMS/HYPOTHESIS: Individuals exposed to maternal diabetes in utero are more likely to develop metabolic and cardiovascular diseases later in life. This may be partially attributable to epigenetic regulation of gene expression. We performed an epigenome-wide association study to examine whether differential DNA methylation, a major source of epigenetic regulation, can be observed in offspring of mothers with type 2 diabetes during the pregnancy (OMD) compared with offspring of mothers with no diabetes during the pregnancy (OMND)...
April 2017: Diabetologia
https://www.readbyqxmd.com/read/27974186/classical-and-non-classical-causes-of-gh-deficiency-in-the-paediatric-age
#20
REVIEW
Natascia Di Iorgi, Giovanni Morana, Anna Elsa Maria Allegri, Flavia Napoli, Roberto Gastaldi, Annalisa Calcagno, Giuseppa Patti, Sandro Loche, Mohamad Maghnie
Growth hormone deficiency (GHD) may result from a failure of hypothalamic GHRH production or release, from congenital disorders of pituitary development, or from central nervous system insults including tumors, surgery, trauma, radiation or infiltration from inflammatory diseases. Idiopathic, isolated GHD is the most common sporadic form of hypopituitarism. GHD may also occur in combination with other pituitary hormone deficiencies, and is often referred to as hypopituitarism, combined pituitary hormone deficiency (CPHD), multiple pituitary hormone deficiency (MPHD) or panhypopituitarism...
December 2016: Best Practice & Research. Clinical Endocrinology & Metabolism
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