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https://www.readbyqxmd.com/read/28533516/asd-restricted-and-repetitive-behaviors-associated-at-17q21-33-genes-prioritized-by-expression-in-fetal-brains
#1
R M Cantor, L Navarro, H Won, R L Walker, J K Lowe, D H Geschwind
Autism spectrum disorder (ASD) is a behaviorally defined condition that manifests in infancy or early childhood as deficits in communication skills and social interactions. Often, restricted and repetitive behaviors (RRBs) accompany this disorder. ASD is polygenic and genetically complex, so we hypothesized that focusing analyses on intermediate core component phenotypes, such as RRBs, can reduce genetic heterogeneity and improve statistical power. Applying this approach, we mined Caucasian genome-wide association studies (GWAS) data from two of the largest ASD family cohorts, the Autism Genetics Resource Exchange and Autism Genome Project (AGP)...
May 23, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28521150/the-effects-of-copper-oxide-nanoparticles-on-dorsoventral-patterning-convergent-extension-and-neural-and-cardiac-development-of-zebrafish
#2
Jia Xu, Qiuping Zhang, Xu Li, Sihui Zhan, Lifeng Wang, Dongyan Chen
Currently, nanoparticles are widely used in biomedicine and industry. CuO nanoparticles (CuO-NPs) are versatile materials in our daily life and their toxicity has drawn extensive attention. In this study, we concentrate on the effect of CuO-NPs on early zebrafish development. The results reveal that CuO-NPs can induce abnormal phenotypes of a smaller head and eyes and delayed epiboly. The gene expression pattern shows that CuO-NPs spatially narrow the expression of dorsal genes chordin and goosecoid and alter the expression of dlx3, ntl and hgg which are related to the cell migration of gastrulation...
May 4, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28515447/dlx3-interacts-with-gcm1-and-inhibits-its-transactivation-stimulating-activity-in-a-homeodomain-dependent-manner-in-human-trophoblast-derived-cells
#3
Sha Li, Mark S Roberson
The placental transcription factors Distal-less 3 (DLX3) and Glial cell missing-1 (GCM1) have been shown to coordinate the specific regulation of PGF in human trophoblast cell lines. While both factors independently have a positive effect on PGF gene expression, when combined, DLX3 acts as an antagonist to GCM. Despite this understanding, potential mechanisms accounting for this regulatory interaction remain unexplored. We identify physical and functional interactions between specific domains of DLX3 and GCM1 in human trophoblast-derived cells by performing immunoprecipitation and mammalian one hybrid assays...
May 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28424525/genome-wide-detection-of-copy-number-variation-in-chinese-indigenous-sheep-using-an-ovine-high-density-600%C3%A2-k-snp-array
#4
Qing Ma, Xuexue Liu, Jianfei Pan, Lina Ma, Yuehui Ma, Xiaohong He, Qianjun Zhao, Yabin Pu, Yingkang Li, Lin Jiang
Copy number variants (CNVs) represent a form of genomic structural variation underlying phenotypic diversity. In this study, we used the Illumina Ovine SNP 600 K BeadChip array for genome-wide detection of CNVs in 48 Chinese Tan sheep. A total of 1,296 CNV regions (CNVRs), ranging from 1.2 kb to 2.3 Mb in length, were detected, representing approximately 4.7% of the entire ovine genome (Oar_v3.1). We combined our findings with five existing CNVR reports to generate a composite genome-wide dataset of 4,321 CNVRs, which revealed 556 (43%) novel CNVRs...
April 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28419554/the-major-mir-31-target-genes-stk40-and-lats2-and-their-implications-in-the-regulation-of-keratinocyte-growth-and-hair-differentiation
#5
Liming Luan, Jianyun Shi, Zhengquan Yu, Thomas Andl
Emerging evidence indicates that even subtle changes in the expression of key genes of signaling pathways can have profound effects. MicroRNAs (miRNAs) are masters of subtleness and generally have only mild effects on their target genes. The microRNA miR-31 is one of the major microRNAs in many cutaneous conditions associated with activated keratinocytes such as the hyperproliferative diseases psoriasis, non-melanoma skin cancer, and hair follicle growth. miR-31 is a marker of the hair growth phase, and in our miR-31 transgenic mouse model it impairs the function of keratinocytes, subsequently leading to aberrant proliferation, apoptosis and differentiation that result in altered hair growth, while loss of miR-31 leads to increased hair growth...
April 17, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28344658/flightless-i-governs-cell-fate-by-recruiting-the-sumo-isopeptidase-senp3-to-distinct-hox-genes
#6
Arnab Nayak, Anja Reck, Christian Morsczeck, Stefan Müller
BACKGROUND: Despite recent studies on the role of ubiquitin-related SUMO modifier in cell fate decisions, our understanding on precise molecular mechanisms of these processes is limited. Previously, we established that the SUMO isopeptidase SENP3 regulates chromatin assembly of the MLL1/2 histone methyltransferase complex at distinct HOX genes, including the osteogenic master regulator DLX3. A comprehensive mechanism that regulates SENP3 transcriptional function was not understood. RESULTS: Here, we identified flightless-I homolog (FLII), a member of the gelsolin family of actin-remodeling proteins, as a novel regulator of SENP3...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28298997/tricho-dento-osseous-syndrome-and-precocious-eruption
#7
Parul Jain, Rahul Kaul, Subrata Saha, Subir Sarkar
Tricho-dento-osseous syndrome (TDO), an uncommon form of ectodermal dysplasia is an autosomal dominant genetic disorder which is characterized by inherited defects in tissues arising from epithelial-mesenchymal interaction. Genetic studies have revealed that it is caused by mutation in the DLX3 gene. TDO presents with a great phenotypic heterogeneity and studies have suggested that this heterogeneity is the result of environmental factors or other genetic modifiers. In this article, we report a case of TDO in which the child had typical clinical features of hair, teeth and bone defects, as seen in TDO...
March 2017: Journal of Clinical and Experimental Dentistry
https://www.readbyqxmd.com/read/28186503/a-novel-dlx3-pkc-integrated-signaling-network-drives-keratinocyte-differentiation
#8
Elisabetta Palazzo, Meghan D Kellett, Christophe Cataisson, Paul W Bible, Shreya Bhattacharya, Hong-Wei Sun, Anna C Gormley, Stuart H Yuspa, Maria I Morasso
Epidermal homeostasis relies on a well-defined transcriptional control of keratinocyte proliferation and differentiation, which is critical to prevent skin diseases such as atopic dermatitis, psoriasis or cancer. We have recently shown that the homeobox transcription factor DLX3 and the tumor suppressor p53 co-regulate cell cycle-related signaling and that this mechanism is functionally involved in cutaneous squamous cell carcinoma development. Here we show that DLX3 expression and its downstream signaling depend on protein kinase C α (PKCα) activity in skin...
April 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28135572/dlx3-mutation-negatively-regulates-odontogenic-differentiation-of-human-dental-pulp-cells
#9
Li Zeng, Na Zhao, Dong Han, Haochen Liu, Yang Liu, Yixiang Wang, Hailan Feng
OBJECTIVES: The purpose of this study was to investigate the role of a novel mutant DLX3 on the odontogenic differentiation of human dental pulp cells (hDPCs) in tricho-dento-osseous (TDO) syndrome. DESIGN: hDPCs were obtained from the healthy premolars, stably-expressing wild-type DLX3 (WT), novel mutant DLX3 (Mu) and control vector (NC) cells were generated using recombinant lentiviruses. The proliferation rates of WT-hDPCs and Mu-hDPCs were measured by CCK8 assay...
May 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/28125839/generation-of-functional-lentoid-bodies-from-human-induced-pluripotent-stem-cells-derived-from-urinary-cells
#10
Qiuli Fu, Zhenwei Qin, Xiuming Jin, Lifang Zhang, Zhijian Chen, Jiliang He, Junfeng Ji, Ke Yao
Purpose: The pathological mechanisms underlying cataract formation remain largely unknown on account of the lack of appropriate in vitro cellular models. The aim of this study is to develop a stable in vitro system for human lens regeneration using pluripotent stem cells. Methods: Isolated human urinary cells were infected with four Yamanaka factors to generate urinary human induced pluripotent stem cells (UiPSCs), which were induced to differentiate into lens progenitor cells and lentoid bodies (LBs)...
January 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27996093/dlx3-and-gcm-1-functionally-coordinate-the-regulation-of-placental-growth-factor-in-human-trophoblast-derived-cells
#11
Sha Li, Mark S Roberson
Placental growth factor (PGF) is abundantly expressed by trophoblast cells within human placentae and is important for trophoblast development and placental vascularization. Circulating maternal serum levels of PGF are dynamically upregulated across gestation in normal pregnancies, whereas low circulating levels and placental production of PGF have been implicated in the pathogenesis of preeclampsia and other gestational diseases. However, the underlying molecular mechanism of regulating PGF expression in the human placenta remains poorly understood...
October 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27924851/senescence-novel-insight-into-dlx3-mutations-leading-to-enhanced-bone-formation-in-tricho-dento-osseous-syndrome
#12
Na Zhao, Dong Han, Haochen Liu, Yue Li, Sing-Wai Wong, Zhengyi Cao, Jian Xu, Xiaowei Zhang, Tao Cai, Yixiang Wang, Hailan Feng
The homeodomain transcription factor distal-less homeobox 3 gene (DLX3) is required for hair, tooth and skeletal development. DLX3 mutations have been found to be responsible for Tricho-Dento-Osseous (TDO) syndrome, characterized by kinky hair, thin-pitted enamel and increased bone density. Here we show that the DLX3 mutation (c.533 A>G; Q178R) attenuates osteogenic potential and senescence of bone mesenchymal stem cells (BMSCs) isolated from a TDO patient, providing a molecular explanation for abnormal increased bone density...
December 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27777986/transcription-factor-dlx3-induces-aryl-hydrocarbon-receptor-promoter-activity
#13
June Ho Shin, Mikel D Haggadone, John B Sunwoo
The Distal-less (Dlx) homeobox transcription factors (TFs) play a prominent role in regulating multiple facets of vertebrate biology. Though widely studied as mediators of tissue development, recent work has uncovered a role for this TF family in modulating the vertebrate hematopoietic compartment. Pertinent to our study, murine Dlx1-3 are expressed in an innate lymphocyte population known as natural killer (NK) cells, and they are implicated to assume a functional role in the NK cell maturation pathway. However, Dlx target genes are poorly understood...
September 2016: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/27760456/dlx3-dependent-regulation-of-ion-transporters-and-carbonic-anhydrases-is-crucial-for-enamel-mineralization
#14
Olivier Duverger, Takahiro Ohara, Paul W Bible, Angela Zah, Maria I Morasso
Patients with tricho-dento-osseous (TDO) syndrome, an ectodermal dysplasia caused by mutations in the homeodomain transcription factor DLX3, exhibit enamel hypoplasia and hypomineralization. Here we used a conditional knockout mouse model to investigate the developmental and molecular consequences of Dlx3 deletion in the dental epithelium in vivo. Dlx3 deletion in the dental epithelium resulted in the formation of chalky hypomineralized enamel in all teeth. Interestingly, transcriptomic analysis revealed that major enamel matrix proteins and proteases known to be involved in enamel secretion and maturation were not affected significantly by Dlx3 deletion in the enamel organ...
October 19, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/27562213/varprism-incorporating-variant-prioritization-in-tests-of-de-novo-mutation-association
#15
Hao Hu, Hilary Coon, Man Li, Mark Yandell, Chad D Huff
BACKGROUND: Patients with certain genetic diseases, such as autism spectrum disorder, have increased rates of de novo mutations within some protein-coding genes. RESULTS: We introduce the VARiant PRIoritization SuM (VARPRISM), a software package which incorporates functional variant prioritization information to improve the power to detect de novo mutations influencing disease risk. VARPRISM evaluates the consequence of any given exonic mutation on the protein sequence to estimate the likelihood that the mutation is benign or damaging and conducts a likelihood ratio test on the gene level...
August 25, 2016: Genome Medicine
https://www.readbyqxmd.com/read/27521061/expression-patterns-of-homeobox-genes-in-the-mouse-vomeronasal-organ-at-postnatal-stages
#16
Isabelle Chang, Marta Parrilla
Homeodomain proteins are encoded by homeobox genes and regulate development and differentiation in many neuronal systems. The mouse vomeronasal organ (VNO) generates in situ mature chemosensory neurons from stem cells. The roles of homeodomain proteins in neuronal differentiation in the VNO are poorly understood. Here we have characterized the expression patterns of 28 homeobox genes in the VNO of C57BL/6 mice at postnatal stages using multicolor fluorescent in situ hybridization. We identified 11 homeobox genes (Dlx3, Dlx4, Emx2, Lhx2, Meis1, Pbx3, Pknox2, Pou6f1, Tshz2, Zhx1, Zhx3) that were expressed exclusively in neurons; 4 homeobox genes (Pax6, Six1, Tgif1, Zfhx3) that were expressed in all non-neuronal cell populations, with Pax6, Six1 and Tgif1 also expressed in some neuronal progenitors and precursors; 12 homeobox genes (Adnp, Cux1, Dlx5, Dlx6, Meis2, Pbx2, Pknox1, Pou2f1, Satb1, Tshz1, Tshz3, Zhx2) with expression in both neuronal and non-neuronal cell populations; and one homeobox gene (Hopx) that was exclusively expressed in the non-sensory epithelium...
July 2016: Gene Expression Patterns: GEP
https://www.readbyqxmd.com/read/27368119/the-parathyroid-hormone-related-protein-is-secreted-during-the-osteogenic-differentiation-of-human-dental-follicle-cells-and-inhibits-the-alkaline-phosphatase-activity-and-the-expression-of-dlx3
#17
C Klingelhöffer, A Reck, T Ettl, C Morsczeck
The dental follicle is involved in tooth eruption and it expresses a great amount of the parathyroid hormone-related protein (PTHrP). PTHrP as an extracellular protein is required for a multitude of different regulations of enchondral bone development and differentiation of bone precursor cells and of the development of craniofacial tissues. The dental follicle contains also precursor cells (DFCs) of the periodontium. Isolated DFCs differentiate into periodontal ligament cells, alveolar osteoblast and cementoblasts...
August 2016: Tissue & Cell
https://www.readbyqxmd.com/read/27243442/expression-of-homeobox-genes-in-the-mouse-olfactory-epithelium
#18
Marta Parrilla, Isabelle Chang, Andrea Degl'Innocenti, Masayo Omura
Homeobox genes constitute a large family of genes widely studied because of their role in the establishment of the body pattern. However, they are also involved in many other events during development and adulthood. The main olfactory epithelium (MOE) is an excellent model to study neurogenesis in the adult nervous system. Analyses of homeobox genes during development show that some of these genes are involved in the formation and establishment of cell diversity in the MOE. Moreover, the mechanisms of expression of odorant receptors (ORs) constitute one of the biggest enigmas in the field...
October 1, 2016: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/27179118/family-based-genetic-association-for-molar-incisor-hypomineralization
#19
Fabiano Jeremias, Ricardo A G Pierri, Juliana F Souza, Camila Maria B Fragelli, Manuel Restrepo, Livia S Finoti, Diego G Bussaneli, Rita C L Cordeiro, Rodrigo Secolin, Claudia V Maurer-Morelli, Raquel M Scarel-Caminaga, Lourdes Santos-Pinto
Despite some evidence of genetic and environmental factors on molar-incisor hypomineralization (MIH), its aetiology remains unclear. This family-based genetic association study aimed more comprehensively to investigate the genetic carriage potentially involved in MIH development. DNA was obtained from buccal cells of 391 individuals who were birth family members of 101 Brazilian nuclear families. Sixty-three single nucleotide polymorphisms (SNPs) were investigated in 21 candidate genes related to amelogenesis using the TaqMan™ OpenArray™ Genotyping platform...
2016: Caries Research
https://www.readbyqxmd.com/read/26921333/mutational-landscape-and-antiproliferative-functions-of-elf-transcription-factors-in-human-cancer
#20
Mizuo Ando, Masahito Kawazu, Toshihide Ueno, Daizo Koinuma, Koji Ando, Junji Koya, Keisuke Kataoka, Takahiko Yasuda, Hiroyuki Yamaguchi, Kazutaka Fukumura, Azusa Yamato, Manabu Soda, Eirin Sai, Yoshihiro Yamashita, Takahiro Asakage, Yasushi Miyazaki, Mineo Kurokawa, Kohei Miyazono, Stephen D Nimer, Tatsuya Yamasoba, Hiroyuki Mano
ELF4 (also known as MEF) is a member of the ETS family of transcription factors. An oncogenic role for ELF4 has been demonstrated in hematopoietic malignancies, but its function in epithelial tumors remains unclear. Here, we show that ELF4 can function as a tumor suppressor and is somatically inactivated in a wide range of human tumors. We identified a missense mutation affecting the transactivation potential of ELF4 in oral squamous cell carcinoma cells. Restoration of the transactivation activity through introduction of wild-type ELF4 significantly inhibited cell proliferation in vitro and tumor xenograft growth...
April 1, 2016: Cancer Research
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