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https://www.readbyqxmd.com/read/28078709/expression-of-transcription-factors-divide-retinal-ganglion-cells-into-distinct-classes
#1
Neal T Sweeney, Kiely N James, Andreea Nistorica, Ryan M Lorig-Roach, David A Feldheim
Retinal ganglion cells (RGCs) are tasked with transmitting all light information from the eye to the retinal recipient areas of the brain. RGCs can be classified into many different types by morphology, gene expression, axonal projections, and functional responses to different light stimuli. Ultimately, these classification systems should be unified into an all-encompassing taxonomy. Toward that end, we show here that nearly all RGCs express either Islet-2, Tbr2 or a combination of Satb1and Satb2. We present gene expression data supporting the hypothesis that Satb1 and Satb2 are expressed in ON-OFF direction-selective (DS) RGCs, complementing our previous work demonstrating that RGCs that express Islet-2 and Tbr2 are non-DS and non-image-forming, respectively...
January 12, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28063930/systematic-time-dependent-visualization-and-quantitation-of-the-neurogenic-rate-in-brain-organoids
#2
Yoichi Kosodo, Taeko Suetsugu, Tetsuya J Kobayashi, Fumio Matsuzaki
Organoids mimicking the formation of the brain cortex have been demonstrated to be powerful tools for developmental studies as well as pathological investigations of brain malformations. Here, we report an integrated approach for the quantification of temporal neural production (neurogenic rate) in organoids derived from embryonic brains. Spherical tissue fragments with polarized cytoarchitectures were incubated in multiple cavities arranged in a polymethylmethacrylate chip. The time-dependent neurogenic rate in the organoids was monitored by the level of EGFP under the promoter of Tbr2, a transcription factor that is transiently expressed in neural fate-committed progenitors during corticogenesis...
January 29, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28057270/the-roles-of-t-box-genes-in-vertebrate-limb-development
#3
C J Sheeba, M P O Logan
Members of the T-box gene family have diverse roles during embryogenesis and many play critical roles in the developing limb. This is exemplified by the fact that, in humans, mutations in T-box genes are associated with several congenital syndromes that include limb defects as part of their characteristic spectrum of abnormalities. T-box genes encode for evolutionary conserved transcription factors that include both transcriptional activators and repressors. The hallmark of T-box gene members is the presence of the eponymous DNA-binding T-box domain...
2017: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/28057268/control-of-neuronal-development-by-t-box-genes-in-the-brain
#4
A B Mihalas, R F Hevner
T-box transcription factors play key roles in the regulation of developmental processes such as cell differentiation and migration. Mammals have 17 T-box genes, of which several regulate brain development. The Tbr1 subfamily of T-box genes is particularly important in development of the cerebral cortex, olfactory bulbs (OBs), and cerebellum. This subfamily is comprised of Tbr1, Tbr2 (also known as Eomes), and Tbx21. In developing cerebral cortex, Tbr2 and Tbr1 are expressed during successive stages of differentiation in the pyramidal neuron lineage, from Tbr2+ intermediate progenitors to Tbr1+ postmitotic glutamatergic neurons...
2017: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/27777416/ap2%C3%AE-controls-adult-hippocampal-neurogenesis-and-modulates-cognitive-but-not-anxiety-or-depressive-like-behavior
#5
A Mateus-Pinheiro, N D Alves, P Patrício, A R Machado-Santos, E Loureiro-Campos, J M Silva, V M Sardinha, J Reis, H Schorle, J F Oliveira, J Ninkovic, N Sousa, L Pinto
Hippocampal neurogenesis has been proposed to participate in a myriad of behavioral responses, both in basal states and in the context of neuropsychiatric disorders. Here, we identify activating protein 2γ (AP2γ, also known as Tcfap2c), originally described to regulate the generation of neurons in the developing cortex, as a modulator of adult hippocampal glutamatergic neurogenesis in mice. Specifically, AP2γ is present in a sub-population of hippocampal transient amplifying progenitors. There, it is found to act as a positive regulator of the cell fate determinants Tbr2 and NeuroD, promoting proliferation and differentiation of new glutamatergic granular neurons...
October 25, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27660277/demyelination-induced-inflammation-attracts-newly-born-neurons-to-the-white-matter
#6
Samah Kalakh, Abdeslam Mouihate
There is compelling evidence that microglial activation negatively impacts neurogenesis. However, microglia have also been shown to promote recruitment of newly born neurons to injured areas of the gray matter. In the present study, we explored whether demyelination-triggered inflammation alters the process of neurogenesis in the white matter. A 2-μl solution of 0.04 % ethidium bromide was stereotaxically injected into the corpus callosum of adult male rats. Brain inflammation was dampened by daily injections of progesterone (5 mg/kg, s...
September 23, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27600842/the-tbr2-molecular-network-controls-cortical-neuronal-differentiation-through-complementary-genetic-and-epigenetic-pathways
#7
Alessandro Sessa, Ernesto Ciabatti, Daniela Drechsel, Luca Massimino, Gaia Colasante, Serena Giannelli, Takashi Satoh, Shizuo Akira, Francois Guillemot, Broccoli Vania
The T-box containing Tbr2 gene encodes for a transcription factor essential for the specification of the intermediate neural progenitors (INPs) originating the excitatory neurons of the cerebral cortex. However, its overall mechanism of action, direct target genes and cofactors remain unknown. Herein, we carried out global gene expression profiling combined with genome-wide binding site identification to determine the molecular pathways regulated by TBR2 in INPs. This analysis led to the identification of novel protein-protein interactions that control multiple features of INPs including cell-type identity, morphology, proliferation and migration dynamics...
September 6, 2016: Cerebral Cortex
https://www.readbyqxmd.com/read/27581449/a-novel-and-multivalent-role-of-pax6-in-cerebellar-development
#8
Joanna Yeung, Thomas J Ha, Douglas J Swanson, Dan Goldowitz
UNLABELLED: Pax6 is a prominent gene in brain development. The deletion of Pax6 results in devastated development of eye, olfactory bulb, and cortex. However, it has been reported that the Pax6-null Sey cerebellum only has minor defects involving granule cells despite Pax6 being expressed throughout cerebellar development. The present work has uncovered a requirement of Pax6 in the development of all rhombic lip (RL) lineages. A significant downregulation of Tbr1 and Tbr2 expression is found in the Sey cerebellum, these are cell-specific markers of cerebellar nuclear (CN) neurons and unipolar brush cells (UBCs), respectively...
August 31, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27478526/an-integrative-microfluidically-supported-in-vitro-model-of-an-endothelial-barrier-combined-with-cortical-spheroids-simulates-effects-of-neuroinflammation-in-neocortex-development
#9
Martin Raasch, Knut Rennert, Tobias Jahn, Claudia Gärtner, Gilbert Schönfelder, Otmar Huber, Andrea E M Seiler, Alexander S Mosig
The development of therapeutic substances to treat diseases of the central nervous system is hampered by the tightness and selectivity of the blood-brain barrier. Moreover, testing of potential drugs is time-consuming and cost-intensive. Here, we established a new microfluidically supported, biochip-based model of the brain endothelial barrier in combination with brain cortical spheroids suitable to detect effects of neuroinflammation upon disruption of the endothelial layer in response to inflammatory signals...
July 2016: Biomicrofluidics
https://www.readbyqxmd.com/read/27403992/an-essential-role-of-svz-progenitors-in-cortical-folding-in-gyrencephalic-mammals
#10
Tomohisa Toda, Yohei Shinmyo, Tung Anh Dinh Duong, Kosuke Masuda, Hiroshi Kawasaki
Because folding of the cerebral cortex in the mammalian brain is believed to be crucial for higher brain functions, the mechanisms underlying its formation during development and evolution are of great interest. Although it has been proposed that increased neural progenitors in the subventricular zone (SVZ) are responsible for making cortical folds, their roles in cortical folding are still largely unclear, mainly because genetic methods for gyrencephalic mammals had been poorly available. Here, by taking an advantage of our newly developed in utero electroporation technique for the gyrencephalic brain of ferrets, we investigated the role of SVZ progenitors in cortical folding...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27347347/pai-1-secretion-of-endometrial-and-endometriotic-cells-is-smad2-3-and-erk1-2-dependent-and-influences-cell-adhesion
#11
Cong Sui, Ezekiel Mecha, Charles Oa Omwandho, Anna Starzinski-Powitz, Angelika Stammler, Hans-Rudolf Tinneberg, Lutz Konrad
In the endometrium transforming growth factor-betas (TGF-βs) are involved mainly in menstruation and endometriosis. After binding of the ligands to the high-affinity receptors, TGF-β receptors (TBR1 and TBR2), TGF-βs activate Smad signaling to modulate gene expression and cellular functions. However, recently also Smad-independent pathways have been studied in more details. To evaluate both pathways, we have analyzed TGF-β signaling in human endometrial and endometriotic cells. Although endometrial and endometriotic cells secrete TGF-β1, secretion by stromal cells was higher compared to epithelial cells...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27346841/maternal-exposure-to-ochratoxin-a-targets-intermediate-progenitor-cells-of-hippocampal-neurogenesis-in-rat-offspring-via-cholinergic-signal-downregulation-and-oxidative-stress-responses
#12
Takeshi Tanaka, Yasuko Hasegawa-Baba, Yousuke Watanabe, Sayaka Mizukami, Yumi Kangawa, Toshinori Yoshida, Makoto Shibutani
To elucidate the developmental exposure effects of ochratoxin A (OTA) on postnatal hippocampal neurogenesis, pregnant SD rats were provided a diet containing 0, 0.12, 0.6, or 3.0ppm OTA from gestation day 6 to day 21 on weaning after delivery. Offspring were maintained through postnatal day (PND) 77 without OTA exposure. At 3.0ppm, offspring of both sexes showed a transient body weight decrease after weaning. Changes in hippocampal neurogenesis-related parameters as measured in male PND 21 offspring were observed at 3...
June 23, 2016: Reproductive Toxicology
https://www.readbyqxmd.com/read/27320921/intermediate-progenitor-cohorts-differentially-generate-cortical-layers-and-require-tbr2-for-timely-acquisition-of-neuronal-subtype-identity
#13
Anca B Mihalas, Gina E Elsen, Francesco Bedogni, Ray A M Daza, Kevyn A Ramos-Laguna, Sebastian J Arnold, Robert F Hevner
Intermediate progenitors (IPs) amplify the production of pyramidal neurons, but their role in selective genesis of cortical layers or neuronal subtypes remains unclear. Using genetic lineage tracing in mice, we find that IPs destined to produce upper cortical layers first appear early in corticogenesis, by embryonic day 11.5. During later corticogenesis, IP laminar fates are progressively limited to upper layers. We examined the role of Tbr2, an IP-specific transcription factor, in laminar fate regulation using Tbr2 conditional mutant mice...
June 28, 2016: Cell Reports
https://www.readbyqxmd.com/read/27144663/brain-insulin-like-growth-factor-i-directs-the-transition-from-stem-cells-to-mature-neurons-during-postnatal-adult-hippocampal-neurogenesis
#14
Vanesa Nieto-Estévez, Carlos O Oueslati-Morales, Lingling Li, James Pickel, Aixa V Morales, Carlos Vicario-Abejón
The specific actions of insulin-like growth factor-I (IGF-I) and the role of brain-derived IGF-I during hippocampal neurogenesis have not been fully defined. To address the influence of IGF-I on the stages of hippocampal neurogenesis, we studied a postnatal/adult global Igf-I knockout (KO) mice (Igf-I(-/-) ) and a nervous system Igf-I conditional KO (Igf-I(Δ/Δ) ). In both KO mice we found an accumulation of Tbr2(+) -intermediate neuronal progenitors, some of which were displaced in the outer granule cell layer (GCL) and the molecular layer (ML) of the dentate gyrus (DG)...
August 2016: Stem Cells
https://www.readbyqxmd.com/read/27112428/the-chromatin-modifying-complex-corest-lsd1-negatively-regulates-notch-pathway-during-cerebral-cortex-development
#15
Cecilia I Lopez, Katherine E Saud, Rodrigo Aguilar, F Andrés Berndt, José Cánovas, Martín Montecino, Manuel Kukuljan
The development of the cerebral cortex is a dynamic and coordinated process in which cell division, cell death, migration and differentiation must be highly regulated to acquire the final architecture and functional competence of the mature organ. Notch pathway is an important regulator of differentiation and it is essential to maintain neural stem cell (NSC) pool. Here we studied the role of epigenetic modulators such as lysine-specific demethylase 1 (LSD1) and its interactor CoREST in the regulation of the Notch pathway activity during the development of the cerebral cortex...
April 25, 2016: Developmental Neurobiology
https://www.readbyqxmd.com/read/26830142/prenatal-%C3%AE-catenin-brn2-tbr2-transcriptional-cascade-regulates-adult-social-and-stereotypic-behaviors
#16
H Belinson, J Nakatani, B A Babineau, R Y Birnbaum, J Ellegood, M Bershteyn, R J McEvilly, J M Long, K Willert, O D Klein, N Ahituv, J P Lerch, M G Rosenfeld, A Wynshaw-Boris
Social interaction is a fundamental behavior in all animal species, but the developmental timing of the social neural circuit formation and the cellular and molecular mechanisms governing its formation are poorly understood. We generated a mouse model with mutations in two Disheveled genes, Dvl1 and Dvl3, that displays adult social and repetitive behavioral abnormalities associated with transient embryonic brain enlargement during deep layer cortical neuron formation. These phenotypes were mediated by the embryonic expansion of basal neural progenitor cells (NPCs) via deregulation of a β-catenin/Brn2/Tbr2 transcriptional cascade...
October 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/26786850/ethanol-induces-cytostasis-of-cortical-basal-progenitors
#17
Amanjot Kaur Riar, Madhusudhanan Narasimhan, Mary Latha Rathinam, George I Henderson, Lenin Mahimainathan
BACKGROUND: Developing brain is a major target for alcohol's actions and neurological/functional abnormalities include microencephaly, reduced frontal cortex, mental retardation and attention-deficits. Previous studies have shown that ethanol altered the lateral ventricular neuroepithelial cell proliferation. However, the effect of ethanol on subventricular basal progenitors which generate majority of the cortical layers is not known. METHODS: We utilized spontaneously immortalized rat brain neuroblasts obtained from cultures of 18-day-old fetal rat cerebral cortices using in vitro ethanol exposures and an in utero binge model...
January 19, 2016: Journal of Biomedical Science
https://www.readbyqxmd.com/read/26758805/crispr-cas9-induced-disruption-of-gene-expression-in-mouse-embryonic-brain-and-single-neural-stem-cells-in-vivo
#18
Nereo Kalebic, Elena Taverna, Stefania Tavano, Fong Kuan Wong, Dana Suchold, Sylke Winkler, Wieland B Huttner, Mihail Sarov
We have applied the CRISPR/Cas9 system in vivo to disrupt gene expression in neural stem cells in the developing mammalian brain. Two days after in utero electroporation of a single plasmid encoding Cas9 and an appropriate guide RNA (gRNA) into the embryonic neocortex of Tis21::GFP knock-in mice, expression of GFP, which occurs specifically in neural stem cells committed to neurogenesis, was found to be nearly completely (≈ 90%) abolished in the progeny of the targeted cells. Importantly, upon in utero electroporation directly of recombinant Cas9/gRNA complex, near-maximal efficiency of disruption of GFP expression was achieved already after 24 h...
March 2016: EMBO Reports
https://www.readbyqxmd.com/read/26621965/effects-of-lipopolysaccharide-and-progesterone-exposures-on-embryonic-cerebral-cortex-development-in-mice
#19
Ashlie A Tronnes, Jenna Koschnitzky, Ray Daza, Jane Hitti, Jan Marino Ramirez, Robert Hevner
Our objective was to determine if progesterone pretreatment could ameliorate the detrimental effects of lipopolysaccharide (LPS)-induced inflammation on cortical neurogenesis. Timed pregnant mouse dams (n = 8) were given intraperitoneal injections of progesterone (42 mg/kg) or vehicle on embryonic day 17.5. Two hours later, mice were given intraperitoneal LPS (140 μg/kg) or vehicle. Mice were sacrificed 16 hours later on embryonic day 18. Two-color immunofluorescence was performed with primary antibodies T-box transcription factor 2 (Tbr2), ionized calcium binding adapter molecule 1 (Iba1), cleaved caspase 3 (CC3), and 5-bromo-2'-deoxyuridine (BrdU)...
June 2016: Reproductive Sciences
https://www.readbyqxmd.com/read/26443441/dynamic-expression-patterns-of-progenitor-and-neuron-layer-markers-in-the-developing-human-dentate-gyrus-and-fimbria
#20
Sara Cipriani, Nathalie Journiac, Jeannette Nardelli, Catherine Verney, Anne-Lise Delezoide, Fabien Guimiot, Pierre Gressens, Homa Adle-Biassette
The molecular mechanisms that orchestrate the development of the human dentate gyrus are not known. In this study, we characterized the formation of human dentate and fimbrial progenitors and postmitotic neurons from 9 gestational weeks (GW9) to GW25. PAX6(+) progenitor cells remained proliferative until GW16 in the dentate ventricular zone. By GW11, the secondary dentate matrix had developed in the intermediate zone, surrounding the dentate anlage and streaming toward the subpial layer. This secondary matrix contained proliferating PAX6(+) and/or TBR2(+) progenitors...
October 5, 2015: Cerebral Cortex
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