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https://www.readbyqxmd.com/read/28798667/the-foxp2-driven-network-in-developmental-disorders-and-neurodegeneration
#1
Franz Oswald, Patricia Klöble, André Ruland, David Rosenkranz, Bastian Hinz, Falk Butter, Sanja Ramljak, Ulrich Zechner, Holger Herlyn
The transcription repressor FOXP2 is a crucial player in nervous system evolution and development of humans and songbirds. In order to provide an additional insight into its functional role we compared target gene expression levels between human neuroblastoma cells (SH-SY5Y) stably overexpressing FOXP2 cDNA of either humans or the common chimpanzee, Rhesus monkey, and marmoset, respectively. RNA-seq led to identification of 27 genes with differential regulation under the control of human FOXP2, which were previously reported to have FOXP2-driven and/or songbird song-related expression regulation...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28741757/equivalent-missense-variant-in-the-foxp2-and-foxp1-transcription-factors-causes-distinct-neurodevelopmental-disorders
#2
Elliot Sollis, Pelagia Deriziotis, Hirotomo Saitsu, Noriko Miyake, Naomichi Matsumoto, Mariëtte J V Hoffer, Claudia A L Ruivenkamp, Mariëlle Alders, Nobuhiko Okamoto, Emilia K Bijlsma, Astrid S Plomp, Simon E Fisher
The closely related paralogues FOXP2 and FOXP1 encode transcription factors with shared functions in the development of many tissues, including the brain. However, while mutations in FOXP2 lead to a speech/language disorder characterized by childhood apraxia of speech (CAS), the clinical profile of FOXP1 variants includes a broader neurodevelopmental phenotype with global developmental delay, intellectual disability, and speech/language impairment. Using clinical whole-exome sequencing, we report an identical de novo missense FOXP1 variant identified in three unrelated patients...
July 25, 2017: Human Mutation
https://www.readbyqxmd.com/read/28692932/axon-guidance-pathways-served-as-common-targets-for-human-speech-language-evolution-and-related-disorders
#3
Huimeng Lei, Zhangming Yan, Xiaohong Sun, Yue Zhang, Jianhong Wang, Caihong Ma, Qunyuan Xu, Rui Wang, Erich D Jarvis, Zhirong Sun
Human and several nonhuman species share the rare ability of modifying acoustic and/or syntactic features of sounds produced, i.e. vocal learning, which is the important neurobiological and behavioral substrate of human speech/language. This convergent trait was suggested to be associated with significant genomic convergence and best manifested at the ROBO-SLIT axon guidance pathway. Here we verified the significance of such genomic convergence and assessed its functional relevance to human speech/language using human genetic variation data...
July 7, 2017: Brain and Language
https://www.readbyqxmd.com/read/28691208/transcriptomic-profile-analysis-of-mouse-neural-tube-development-by-rna-seq
#4
Juan Yu, Jianbing Mu, Qian Guo, Lihong Yang, Juan Zhang, Zhizhen Liu, Baofeng Yu, Ting Zhang, Jun Xie
The neural tube is the primordium of the central nervous system (CNS) in which its development is not entirely clear. Understanding the cellular and molecular basis of neural tube development could, therefore, provide vital clues to the mechanism of neural tube defects (NTDs). Here, we investigated the gene expression profiles of three different time points (embryonic day (E) 8.5, 9.5 and 10.5) of mouse neural tube by using RNA-seq approach. About 391 differentially expressed genes (DEGs) were screened during mouse neural tube development, including 45 DEGs involved in CNS development, among which Bmp2, Ascl1, Olig2, Lhx1, Wnt7b and Eomes might play the important roles...
July 10, 2017: IUBMB Life
https://www.readbyqxmd.com/read/28687613/valproic-acid-induces-aberrant-development-of-striatal-compartments-and-corticostriatal-pathways-in-a-mouse-model-of-autism-spectrum-disorder
#5
Hsiao-Ying Kuo, Fu-Chin Liu
The striatum comprises two neurochemical compartments: striosomes and the matrix. Striosomal and matrix compartments receive inputs from limbic-related and sensorimotor cortices, respectively. Here, we investigate the impact on the corticostriosomal pathway in the valproic acid (VPA)-induced autism spectrum disorder mouse model. VPA administration during the neurogenesis time windows of striosomes, but not the matrix, resulted in aberrant compartmentation [i.e., maternal VPA injections at embryonic day (E)12...
July 7, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28647514/aqueous-cigarette-tar-extracts-disrupt-corticogenesis-from-human-embryonic-stem-cells-in-vitro
#6
Aynun N Begum, Jose S Aguilar, Yiling Hong
BACKGROUND: Cigarette butts are the most common form of litter in the world, and approximately 4.5 trillion smoked cigarettes are discarded every year worldwide. Cigarette butts contain over 4000 chemicals, many of which are known to have neurotoxic effects. Stem cell neuronal differentiation provides an excellent cellular model with which to examine the impact of aqueous cigarette tar extracts (ACTEs) on neurodevelopment. METHODS: We have developed a neurosphere-based stem cell neuronal differentiation protocol that can recapitulate corticogenesis and produce cell types that are similar to upper and lower layer cortical projection neurons found in the germinal zone of the developing human cortex...
June 22, 2017: Environmental Research
https://www.readbyqxmd.com/read/28609679/segregating-polymorphisms-of-foxp2-are-associated-with-measures-of-inner-speech-speech-fluency-and-strength-of-handedness-in-a-healthy-population
#7
Bernard Crespi, Silven Read, Peter Hurd
We genotyped a healthy population for three haplotype-tagging FOXP2 SNPs, and tested for associations of these SNPs with strength of handedness and questionnaire-based metrics of inner speech characteristics (ISP) and speech fluency (FLU), as derived from the Schizotypal Personality Questionnaire-BR. Levels of mixed-handedness were positively correlated with ISP and FLU, supporting prior work on these two domains. Genotype for rs7799109, a SNP previously linked with lateralization of left frontal regions underlying language, was associated with degree of mixed handedness and with scores for ISP and FLU phenotypes...
June 10, 2017: Brain and Language
https://www.readbyqxmd.com/read/28608288/substance-p-effects-exclusively-on-prototypic-neurons-in-mouse-globus-pallidus
#8
Kazuko Mizutani, Susumu Takahashi, Shinichiro Okamoto, Fuyuki Karube, Fumino Fujiyama
Previous studies have suggested that the neurokinin-1 receptor (NK-1R) expressing neurons in the globus pallidus (GP) receive substance P (SP), presumably released by axon collaterals of striatal direct neurons. However, the effect of SP on the GP remains unclear. In this study, we identified that the SP-responsive cells comprise a highly specific cell type in the GP with regard to immunofluorescence, electrophysiology, and projection properties. Morphologically, NK-1R-immunoreactive neurons occasionally co-expressed parvalbumin (PV) and/or Lim-homeobox 6 (Lhx6), but not Forkhead box protein P2 (FoxP2), which is mainly expressed by arkypallidal neurons...
June 12, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/28507505/protein-protein-interaction-among-the-foxp-family-members-and-their-regulation-of-two-target-genes-vldlr-and-cntnap2-in-the-zebra-finch-song-system
#9
Ezequiel Mendoza, Constance Scharff
The Forkhead transcription factor FOXP2 is implicated in speech perception and production. The avian homolog, FoxP2 contributes to song learning and production in birds. In human cell lines, transcriptional activity of FOXP2 requires homo-dimerization or dimerization with paralogs FOXP1 or FOXP4. Whether FoxP dimerization occurs in the brain is unknown. We recently showed that FoxP1, FoxP2 and FoxP4 (FoxP1/2/4) proteins are co-expressed in neurons of Area X, a song control region in zebra finches. We now report on dimer- and oligomerization of zebra finch FoxPs and how this affects transcription...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28488276/cntnap2-is-a-direct-foxp2-target-in-vitro-and-in-vivo-in-zebra-finches-complex-regulation-by-age-and-activity
#10
I Adam, E Mendoza, U Kobalz, S Wohlgemuth, C Scharff
Mutations of FOXP2 are associated with altered brain structure, including the striatal part of the basal ganglia, and cause a severe speech and language disorder. Songbirds serve as a tractable neurobiological model for speech and language research. Experimental downregulation of FoxP2 in zebra finch Area X, a nucleus of the striatal song control circuitry, affects synaptic transmission and spine densities. It also renders song learning and production inaccurate and imprecise, similar to the speech impairment of patients carrying FOXP2 mutations...
May 10, 2017: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/28436202/a-common-genetic-variant-in-foxp2-is-associated-with-language-based-learning-dis-abilities-evidence-from-two-italian-independent-samples
#11
Alessandra Mozzi, Valentina Riva, Diego Forni, Manuela Sironi, Cecilia Marino, Massimo Molteni, Stefania Riva, Franca R Guerini, Mario Clerici, Rachele Cagliani, Sara Mascheretti
Language-based Learning Disabilities (LLDs) encompass a group of complex, comorbid, and developmentally associated deficits in communication. Language impairment and developmental dyslexia (DD) represent the most recognized forms of LLDs. Substantial genetic correlations exist between language and reading (dis)abilities. Common variants in the FOXP2 gene were consistently associated with language- and reading-related neuropsychological and neuroanatomical phenotypes. We tested the effect of a FOXP2 common variant, that is, rs6980093 (A/G), on quantitative measures of language and reading in two independent Italian samples: a population-based cohort of 699 subjects (3-11 years old) and a sample of 572 children with DD (6-18 years old)...
April 24, 2017: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
https://www.readbyqxmd.com/read/28421313/association-between-forkhead-box-p2-gene-polymorphism-and-clinical-symptoms-in-chronic-schizophrenia-in-a-chinese-population
#12
Wenwang Rao, Xiangdong Du, Yingyang Zhang, Qiong Yu, Li Hui, Yaqin Yu, Changgui Kou, Guangzhong Yin, Xiaomin Zhu, Lijuan Man, Jair C Soares, Xiang Yang Zhang
The forkhead-box P2 (FOXP2) gene polymorphism has been reported to be involved in the susceptibility to schizophrenia; however, few studies have investigated the association between FOXP2 gene polymorphism and clinical symptoms in schizophrenia. This study investigated whether the FOXP2 gene was associated with the development and symptoms of schizophrenia in relatively genetically homogeneous Chinese population. The FOXP2 rs10447760 polymorphism was genotyped in 1069 schizophrenia inpatients and 410 healthy controls using a case-control design...
April 18, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28340519/barrington-s-nucleus-neuroanatomic-landscape-of-the-mouse-pontine-micturition-center
#13
Anne M J Verstegen, Veronique Vanderhorst, Paul A Gray, Mark L Zeidel, Joel C Geerling
Barrington's nucleus (Bar) is thought to contain neurons that trigger voiding and thereby function as the "pontine micturition center." Lacking detailed information on this region in mice, we examined gene and protein markers to characterize Bar and the neurons surrounding it. Like rats and cats, mice have an ovoid core of medium-sized Bar neurons located medial to the locus coeruleus (LC). Bar neurons express a GFP reporter for Vglut2, develop from a Math1/Atoh1 lineage, and exhibit immunoreactivity for NeuN...
July 1, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28315294/neuronal-cell-sheet-of-cortical-motor-neuron-phenotype-derived-from-human-ips-cells
#14
Noboru Suzuki, Nagisa Arimitsu, Jun Shimizu, Kenji Takai, Chieko Hirotsu, Erika Takada, Yuji Ueda, Sueshige Wakisaka, Naruyoshi Fujiwara, Tomoko Suzuki
<p>Transplantation of stem cells which differentiate into more mature neural cells brings about functional improvement in pre-clinical studies of stroke. Previous transplant approaches in diseased brain have utilized injection of the cells in a cell suspension. In addition, neural stem cells were preferentially used as graft. However, these cells had no specific relationship to the damaged tissue of stroke patients and brain injury. The injection of cells in a suspension destroyed the cell-cell interactions that are suggested to be important for promoting functional integrity as cortical motor neurons...
March 17, 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28265091/conserved-forkhead-dimerization-motif-controls-dna-replication-timing-and-spatial-organization-of-chromosomes-in-s-cerevisiae
#15
A Zachary Ostrow, Reza Kalhor, Yan Gan, Sandra K Villwock, Christian Linke, Matteo Barberis, Lin Chen, Oscar M Aparicio
Forkhead Box (Fox) proteins share the Forkhead domain, a winged-helix DNA binding module, which is conserved among eukaryotes from yeast to humans. These sequence-specific DNA binding proteins have been primarily characterized as transcription factors regulating diverse cellular processes from cell cycle control to developmental fate, deregulation of which contributes to developmental defects, cancer, and aging. We recently identified Saccharomyces cerevisiae Forkhead 1 (Fkh1) and Forkhead 2 (Fkh2) as required for the clustering of a subset of replication origins in G1 phase and for the early initiation of these origins in the ensuing S phase, suggesting a mechanistic role linking the spatial organization of the origins and their activity...
March 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28257525/foxp-in-tetrapoda-intrinsically-disordered-regions-short-linear-motifs-and-their-evolutionary-significance
#16
Lucas Henriques Viscardi, Luciana Tovo-Rodrigues, Pamela Paré, Nelson Jurandi Rosa Fagundes, Francisco Mauro Salzano, Vanessa Rodrigues Paixão-Côrtes, Claiton Henrique Dotto Bau, Maria Cátira Bortolini
The FOXP subfamily is probably the most extensively characterized subfamily of the forkhead superfamily, playing important roles in development and homeostasis in vertebrates. Intrinsically disorder protein regions (IDRs) are protein segments that exhibit multiple physical interactions and play critical roles in various biological processes, including regulation and signaling. IDRs in proteins may play an important role in the evolvability of genetic systems. In this study, we analyzed 77 orthologous FOXP genes/proteins from Tetrapoda, regarding protein disorder content and evolutionary rate...
January 2017: Genetics and Molecular Biology
https://www.readbyqxmd.com/read/28244870/embryonic-transcription-factor-expression-in-mice-predicts-medial-amygdala-neuronal-identity-and-sex-specific-responses-to-innate-behavioral-cues
#17
Julieta E Lischinsky, Katie Sokolowski, Peijun Li, Shigeyuki Esumi, Yasmin Kamal, Meredith Goodrich, Livio Oboti, Timothy R Hammond, Meera Krishnamoorthy, Daniel Feldman, Molly Huntsman, Judy Liu, Joshua G Corbin
The medial subnucleus of the amygdala (MeA) plays a central role in processing sensory cues required for innate behaviors. However, whether there is a link between developmental programs and the emergence of inborn behaviors remains unknown. Our previous studies revealed that the telencephalic preoptic area (POA) embryonic niche is a novel source of MeA destined progenitors. Here, we show that the POA is comprised of distinct progenitor pools complementarily marked by the transcription factors Dbx1 and Foxp2...
March 13, 2017: ELife
https://www.readbyqxmd.com/read/28179876/talking-convergence-growing-evidence-links-foxp2-and-retinoic-acid-in-shaping-speech-related-motor-circuitry
#18
COMMENT
Moritz Negwer, Dirk Schubert
No abstract text is available yet for this article.
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28112643/layer-specific-chromatin-accessibility-landscapes-reveal-regulatory-networks-in-adult-mouse-visual-cortex
#19
Lucas T Gray, Zizhen Yao, Thuc Nghi Nguyen, Tae Kyung Kim, Hongkui Zeng, Bosiljka Tasic
Mammalian cortex is a laminar structure, with each layer composed of a characteristic set of cell types with different morphological, electrophysiological, and connectional properties. Here, we define chromatin accessibility landscapes of major, layer-specific excitatory classes of neurons, and compare them to each other and to inhibitory cortical neurons using the Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq). We identify a large number of layer-specific accessible sites, and significant association with genes that are expressed in specific cortical layers...
January 23, 2017: ELife
https://www.readbyqxmd.com/read/28104810/the-foxp2-forkhead-domain-binds-to-a-variety-of-dna-sequences-with-different-rates-and-affinities
#20
Helen Webb, Olga Steeb, Ashleigh Blane, Lia Rotherham, Shaun Aron, Phillip Machanick, Heini Dirr, Sylvia Fanucchi
FOXP2 is a member of the P subfamily of FOX transcription factors, the DNA binding domain of which is the winged helix forkhead domain. In this work we show that the FOXP2 forkhead domain is able to bind to various DNA sequences, including a novel sequence identified in this work, with different affinities and rates as detected using surface plasmon resonance. Combining the experimental work with molecular docking, we show that high affinity sequences remain bound to the protein for longer, form a greater number of interactions with the protein and induce a greater structural change in the protein than low affinity sequences...
January 18, 2017: Journal of Biochemistry
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