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https://www.readbyqxmd.com/read/29288087/the-tbr1-related-autistic-spectrum-disorder-phenotype-and-its-clinical-spectrum
#1
J H McDermott, D D D Study, J Clayton-Smith, T A Briggs
A diverse range of genetic aberrations can lead to Autistic Spectrum Disorder (ASD) and many of these have been identified via Next Generation Sequencing (NGS) as part of large scale consortium studies. ASD is a phenotypically variable disorder and detailed clinical descriptions are essential to appreciate genotype-phenotype relationships. In this report, we provide a comprehensive clinical description of a child with ASD in whom a TBR1 variant was identified. We review this case in the context of the current TBR1 literature and highlight the variable spectrum of disease associated with this gene...
December 26, 2017: European Journal of Medical Genetics
https://www.readbyqxmd.com/read/29273633/otx1-regulates-cell-cycle-progression-of-neural-progenitors-in-the-developing-cerebral-cortex
#2
Baoshan Huang, Xue Li, Xiaomeng Tu, Wei Zhao, Dan Zhu, Yue Feng, Xiang Si, Jie-Guang Chen
The progenitor cells in the cerebral cortex coordinate proliferation and mitotic exit to generate the correct number of neurons and glial cells during development. However, mechanisms for regulating the mitotic cycle of cortical progenitors are not fully understood. Otx1 is one of the homeobox-containing transcription factors frequently implicated in the development of the central nervous system. Mice bearing a targeted deletion of Otx1 exhibit brain hypoplasia and a decrease in the number of cortical neurons...
December 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29259547/a-radial-glia-fascicle-leads-principal-neurons-from-the-pallial-subpallial-boundary-into-the-developing-human-insula
#3
Emilio González-Arnay, Miriam González-Gómez, Gundela Meyer
The human insular lobe, in the depth of the Sylvian fissure, displays three main cytoarchitectonic divisions defined by the differentiation of granular layers II and IV. These comprise a rostro-ventral agranular area, an intermediate dysgranular area, and a dorso-caudal granular area. Immunohistochemistry in human embryos and fetuses using antibodies against PCNA, Vimentin, Nestin, Tbr1, and Tb2 reveals that the insular cortex is unique in that it develops far away from the ventricular zone (VZ), with most of its principal neurons deriving from the subventricular zone (SVZ) of the pallial-subpallial boundary (PSB)...
2017: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/29217680/non-newly-generated-immature-neurons-in-the-sheep-brain-are-not-restricted-to-cerebral-cortex
#4
Matteo Piumatti, Ottavia Palazzo, Chiara La Rosa, Paola Crociara, Roberta Parolisi, Federico Luzzati, Frederic Lévy, Luca Bonfanti
A newly proposed form of brain structural plasticity consists of non-newly generated, "immature" neurons of the adult cerebral cortex. Similar to newly generated neurons, these cells express the cytoskeletal protein Doublecortin (DCX), yet they are generated prenatally, then remaining in a state of immaturity for long periods. In rodents, the immature neurons are restricted to the paleocortex, whereas in other mammals are found also in neocortex. Here, we analyzed the DCX-expressing cells in the whole sheep brain of both sexes, to search for an indicator of structural plasticity at a cellular level in a relatively large-brained, long-living mammal...
December 7, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29205104/coup-tf1-modulates-thyroid-hormone-action-in-an-embryonic-stem-cell-model-of-cortical-pyramidal-neuronal-differentiation
#5
Xiaochun Teng, Yan-Yun Liu, Weiping Teng, Gregory A Brent
BACKGROUND: Thyroid hormone is critical for normal brain development and acts in a spatial and temporal specific pattern. Thyroid hormone excess, or deficiency, can lead to irreversible impairment of brain and sensory development. COUP-TF1, expressed early in neuronal development, is essential to achieve normal brain structure. Thyroid hormone stimulation of gene expression is inversely correlated with the level of COUP-TF1 expression. METHODS: We utilized an in vitro method of differentiating mouse embryonic stem (mES) cells into cortical neurons to study the influence of COUP-TF1 on thyroid hormone signaling in brain development...
December 5, 2017: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/29160172/neural-differentiation-of-spheroids-derived-from-hipsc-msc-co-culture
#6
Liqing Song, Ang-Chen Tsai, Xuegang Yuan, Julie Bejoy, Sébastien Sart, Teng Ma, Yan Li
Organoids, the condensed 3-D tissues emerged at the early stage of organogenesis, are a promising approach to regenerate functional and vascularized organ mimics. While incorporation of heterotypic cell types such as human mesenchymal stem cells (hMSCs) and human induced pluripotent stem cells (hiPSCs) derived neural progenitors aid neural organ development, the interactions of secreted factors during neurogenesis have not been well understood. The objective of this study is to investigate the impact of the composition and structure of 3-D hybrid spheroids of hiPSCs and hMSCs on dorsal cortical differentiation and the secretion of extracellular matrices and trophic factors in vitro...
November 21, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/29128818/comparison-of-2d-and-3d-neural-induction-methods-for-the-generation-of-neural-progenitor-cells-from-human-induced-pluripotent-stem-cells
#7
Abinaya Chandrasekaran, Hasan X Avci, Anna Ochalek, Lone N Rösingh, Kinga Molnár, Lajos László, Tamás Bellák, Annamária Téglási, Krisztina Pesti, Arpad Mike, Phetcharat Phanthong, Orsolya Bíró, Vanessa Hall, Narisorn Kitiyanant, Karl-Heinz Krause, Julianna Kobolák, András Dinnyés
Neural progenitor cells (NPCs) from human induced pluripotent stem cells (hiPSCs) are frequently induced using 3D culture methodologies however, it is unknown whether spheroid-based (3D) neural induction is actually superior to monolayer (2D) neural induction. Our aim was to compare the efficiency of 2D induction with 3D induction method in their ability to generate NPCs, and subsequently neurons and astrocytes. Neural differentiation was analysed at the protein level qualitatively by immunocytochemistry and quantitatively by flow cytometry for NPC (SOX1, PAX6, NESTIN), neuronal (MAP2, TUBB3), cortical layer (TBR1, CUX1) and glial markers (SOX9, GFAP, AQP4)...
October 14, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28939666/the-e2a-splice-variant-e47-regulates-the-differentiation-of-projection-neurons-via-p57-kip2-during-cortical-development
#8
Sabrina Pfurr, Yu-Hsuan Chu, Christian Bohrer, Franziska Greulich, Robert Beattie, Könül Mammadzada, Miriam Hils, Sebastian J Arnold, Verdon Taylor, Kristina Schachtrup, N Henriette Uhlenhaut, Christian Schachtrup
During corticogenesis, distinct classes of neurons are born from progenitor cells located in the ventricular and subventricular zones, from where they migrate towards the pial surface to assemble into highly organized layer-specific circuits. However, the precise and coordinated transcriptional network activity defining neuronal identity is still not understood. Here, we show that genetic depletion of the basic helix-loop-helix (bHLH) transcription factor E2A splice variant E47 increased the number of Tbr1-positive deep layer and Satb2-positive upper layer neurons at E14...
September 22, 2017: Development
https://www.readbyqxmd.com/read/28891227/expression-of-regulatory-genes-in-the-embryonic-brain-of-a-lizard-and-implications-for-understanding-pallial-organization-and-evolution
#9
Ester Desfilis, Antonio Abellán, Vicente Sentandreu, Loreta Medina
The comparison of gene expression patterns in the embryonic brain of mouse and chicken is being essential for understanding pallial organization. However, the scarcity of gene expression data in reptiles, crucial for understanding evolution, makes it difficult to identify homologues of pallial divisions in different amniotes. We cloned and analyzed the expression of the genes Emx1, Lhx2, Lhx9, and Tbr1 in the embryonic telencephalon of the lacertid lizard Psammodromus algirus. The comparative expression patterns of these genes, critical for pallial development, are better understood when using a recently proposed six-part model of pallial divisions...
September 11, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28833756/multinodular-and-vacuolating-neuronal-tumors-in-epilepsy-dysplasia-or-neoplasia
#10
Maria Thom, Joan Liu, Anika Bongaarts, Roy J Reinten, Beatrice Paradiso, Hans Rolf Jäger, Cheryl Reeves, Alyma Somani, Shu An, Derek Marsdon, Andrew McEvoy, Anna Miserocchi, Lewis Thorne, Fay Newman, Sorin Bucur, Mrinalini Honavar, Tom Jacques, Eleonora Aronica
Multinodular and vacuolating neuronal tumor (MVNT) is a new pattern of neuronal tumour included in the recently revised WHO 2016 classification of tumors of the CNS. There are 15 reports in the literature to date. They are typically associated with late onset epilepsy and a neoplastic vs. malformative biology has been questioned. We present a series of ten cases and compare their pathological and genetic features to better characterized epilepsy-associated malformations including focal cortical dysplasia type II (FCDII) and low-grade epilepsy-associated tumors (LEAT)...
August 19, 2017: Brain Pathology
https://www.readbyqxmd.com/read/28726548/wnt-yes-associated-protein-interactions-during-neural-tissue-patterning-of-human-induced-pluripotent-stem-cells
#11
Julie Bejoy, Liqing Song, Yi Zhou, Yan Li
Human induced pluripotent stem cells (hiPSCs) have special ability to self-assemble into neural spheroids or mini-brain-like structures. During the self-assembly process, Wnt signaling plays an important role in regional patterning and establishing positional identity of hiPSC-derived neural progenitors. Recently, the role of Wnt signaling in regulating Yes-associated protein (YAP) expression (nuclear or cytoplasmic), the pivotal regulator during organ growth and tissue generation, has attracted increasing interests...
August 31, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28677231/development-of-deep-and-upper-neuronal-layers-in-the-domestic-cat-sheep-and-pig-neocortex
#12
M Glatzle, M Hoops, J Kauffold, J Seeger, S A Fietz
The neocortex plays a key role in cognition, volitional motor control and sensory perception and has undergone tremendous expansion during evolution. The mature neocortex consists of radially aligned neurons that are arranged in six layers. Layers II-VI are often split into two groups: deep and upper layers, both building up the so-called cortical plate during embryonic and foetal development. So far cortical neurogenesis, including the generation of deep and upper layers, has mostly been studied in laboratory rodents and primates...
July 4, 2017: Anatomia, Histologia, Embryologia
https://www.readbyqxmd.com/read/28647514/aqueous-cigarette-tar-extracts-disrupt-corticogenesis-from-human-embryonic-stem-cells-in-vitro
#13
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...
October 2017: Environmental Research
https://www.readbyqxmd.com/read/28607372/enhanced-derivation-of-human-pluripotent-stem-cell-derived-cortical-glutamatergic-neurons-by-a-small-molecule
#14
Shi-Ying Cao, Yao Hu, Cheng Chen, Fang Yuan, Min Xu, Qi Li, Kai-Heng Fang, Yaoyu Chen, Yan Liu
Human pluripotent stem cells (hPSCs) play important role in studying the function of human glutamatergic neurons and related disease pathogenesis. However, the current hPSC-derived cortical system produced a significant number of inhibitory GABAergic neurons that reduced the purity of excitatory neurons. In this study, we established a robust hPSC-derived cortical neurogenesis system by applying the SHH inhibitor cyclopamine. Cyclopamine specified the dorsal cortical fate in a dose-dependent manner and enhanced the generation of cortical glutamatergic neurons, expressing PAX6, TBR1, TBR2, CTIP2, SATB2, and vesicular glutamate transporters (vGLUT)...
June 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28595950/luteolin-attenuates-interleukin-6-mediated-astrogliosis-in-human-ipsc-derived-neural-aggregates-a-candidate-preventive-substance-for-maternal-immune-activation-induced-abnormalities
#15
Masashi Zuiki, Tomohiro Chiyonobu, Michiko Yoshida, Hiroshi Maeda, Satoshi Yamashita, Satoshi Kidowaki, Tatsuji Hasegawa, Hitoshi Gotoh, Tadashi Nomura, Katsuhiko Ono, Hajime Hosoi, Masafumi Morimoto
Maternal infection during pregnancy increases the risk of neurodevelopmental conditions such as autism spectrum disorders and schizophrenia in offspring. Several previous animal studies have indicated that maternal immune activation (MIA), rather than a specific pathogen, alters fetal brain development. Among them, prenatal exposure to interleukin-6 (IL-6) has been associated with behavioral and neuropathological abnormalities, though such findings remain to be elucidated in humans. We developed a human cell-based model of MIA by exposing human induced pluripotent stem cells (hiPSCs)-derived neural aggregates to IL-6 and investigated whether luteolin-a naturally occurring flavonoid found in edible plants-could prevent MIA-induced abnormalities...
July 13, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28586483/isolated-mitochondria-transfer-improves-neuronal-differentiation-of-schizophrenia-derived-induced-pluripotent-stem-cells-and-rescues-deficits-in-a-rat-model-of-the-disorder
#16
Odile Robicsek, Hila M Ene, Rachel Karry, Ofer Ytzhaki, Eyal Asor, Donna McPhie, Bruce M Cohen, Rotem Ben-Yehuda, Ina Weiner, Dorit Ben-Shachar
Dysfunction of mitochondria, key players in various essential cell processes, has been repeatedly reported in schizophrenia (SZ). Recently, several studies have reported functional recovery and cellular viability following mitochondrial transplantation, mostly in ischemia experimental models. Here, we aimed to demonstrate beneficial effects of isolated active normal mitochondria (IAN-MIT) transfer in vitro and in vivo, using SZ-derived induced pluripotent stem cells (iPSCs) differentiating into glutamatergic neuron, as well as a rodent model of SZ...
June 6, 2017: Schizophrenia Bulletin
https://www.readbyqxmd.com/read/28584888/autism-spectrum-disorder-neuropathology-and-animal-models
#17
REVIEW
Merina Varghese, Neha Keshav, Sarah Jacot-Descombes, Tahia Warda, Bridget Wicinski, Dara L Dickstein, Hala Harony-Nicolas, Silvia De Rubeis, Elodie Drapeau, Joseph D Buxbaum, Patrick R Hof
Autism spectrum disorder (ASD) has a major impact on the development and social integration of affected individuals and is the most heritable of psychiatric disorders. An increase in the incidence of ASD cases has prompted a surge in research efforts on the underlying neuropathologic processes. We present an overview of current findings in neuropathology studies of ASD using two investigational approaches, postmortem human brains and ASD animal models, and discuss the overlap, limitations, and significance of each...
October 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28584103/neurog2-and-ascl1-together-regulate-a-postmitotic-derepression-circuit-to-govern-laminar-fate-specification-in-the-murine-neocortex
#18
Daniel J Dennis, Grey Wilkinson, Saiqun Li, Rajiv Dixit, Lata Adnani, Anjali Balakrishnan, Sisu Han, Christopher Kovach, Nicole Gruenig, Deborah M Kurrasch, Richard H Dyck, Carol Schuurmans
A derepression mode of cell-fate specification involving the transcriptional repressors Tbr1, Fezf2, Satb2, and Ctip2 operates in neocortical projection neurons to specify six layer identities in sequence. Less well understood is how laminar fate transitions are regulated in cortical progenitors. The proneural genes Neurog2 and Ascl1 cooperate in progenitors to control the temporal switch from neurogenesis to gliogenesis. Here we asked whether these proneural genes also regulate laminar fate transitions. Several defects were observed in the derepression circuit in Neurog2(-/-);Ascl1(-/-) mutants: an inability to repress expression of Tbr1 (a deep layer VI marker) during upper-layer neurogenesis, a loss of Fezf2(+)/Ctip2(+) layer V neurons, and precocious differentiation of normally late-born, Satb2(+) layer II-IV neurons...
June 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28472243/the-subpial-granular-layer-and-transient-versus-persisting-cajal-retzius-neurons-of-the-fetal-human-cortex
#19
Gundela Meyer, Miriam González-Gómez
Neurons of the subpial granular layer (SGL) in the human marginal zone (MZ) migrate tangentially from the periolfactory subventricular zone all over the neocortex. After an immature stage, from 14 to 18 gestational weeks (GW), the SGL attains maximum prominence around midgestation. At 20-25 GW, a transient miniature cell type in the MZ expresses glutamate decarboxylase (GAD) and calretinin, and extends a varicose plexus surrounding somata of large transient Cajal-Retzius neurons (tCRN), potentially modulating their activity...
May 4, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28419903/dna-methylation-based-age-prediction-from-saliva-high-age-predictability-by-combination-of-7-cpg-markers
#20
Sae Rom Hong, Sang-Eun Jung, Eun Hee Lee, Kyoung-Jin Shin, Woo Ick Yang, Hwan Young Lee
DNA methylation is currently one of the most promising age-predictive biomarkers. Many studies have reported DNA methylation-based age predictive models, but most of these are based on DNA methylation patterns from blood. Only a few studies have examined age-predictive DNA patterns in saliva, which is one of the most frequently-encountered body fluids at crime scenes. In this study, we generated genome-wide DNA methylation profiles of saliva from 54 individuals and identified CpG markers that showed a high correlation between methylation and age...
July 2017: Forensic Science International. Genetics
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