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https://www.readbyqxmd.com/read/28607372/enhanced-derivation-of-human-pluripotent-stem-cell-derived-cortical-glutamatergic-neurons-by-a-small-molecule
#1
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/28583079/lateral-cortical-cdca7-expression-levels-are-regulated-by-pax6-and-influence-the-production-of-intermediate-progenitors
#2
Yu-Ting Huang, John O Mason, David J Price
BACKGROUND: We studied whether regulation of Cdca7 (Cell division cycle associated 7) expression by transcription factor Pax6 contributes to Pax6's cellular actions during corticogenesis. The function of Cdca7 in mediating Pax6's effects during corticogenesis has not been explored. Pax6 is expressed by radial glial progenitors in the ventricular zone of the embryonic cortical neuroepithelium, where it is required for the development of a normal complement of Tbr2-expressing intermediate progenitor cells in the subventricular zone...
June 5, 2017: BMC Neuroscience
https://www.readbyqxmd.com/read/28578005/isolation-characterization-and-differentiation-of-multipotent-neural-progenitor-cells-from-human-cerebrospinal-fluid-in-fetal-cystic-myelomeningocele
#3
Mario Marotta, Alejandra Fernández-Martín, Marc Oria, Cesar G Fontecha, Carles Giné, Vicente Martínez-Ibáñez, Elena Carreras, Michael A Belfort, Gloria Pelizzo, Jose L Peiró
Despite benefits of prenatal in utero repair of myelomeningocele, a severe type of spina bifida aperta, many of these patients will still suffer mild to severe impairment. One potential source of stem cells for new regenerative medicine-based therapeutic approaches for spinal cord injury repair is neural progenitor cells (NPCs) in cerebrospinal fluid (CSF). To this aim, we extracted CSF from the cyst surrounding the exposed neural placode during the surgical repair of myelomeningocele in 6 fetuses (20 to 26weeks of gestation)...
May 15, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28547531/neonatal-hyperoxia-perturbs-neuronal-development-in-the-cerebellum
#4
Till Scheuer, Yuliya Sharkovska, Victor Tarabykin, Katharina Marggraf, Vivien Brockmöller, Christoph Bührer, Stefanie Endesfelder, Thomas Schmitz
Impaired postnatal brain development of preterm infants often results in neurological deficits. Besides pathologies of the forebrain, maldeveolopment of the cerebellum is increasingly recognized to contribute to psychomotor impairments of many former preterm infants. However, causes are poorly defined. We used a hyperoxia model to define neonatal damage in cerebellar granule cell precursors (GCPs) and in Purkinje cells (PCs) known to be essential for interaction with GCPs during development. We exposed newborn rats to 24 h 80% O2 from age P6 to P7 to identify postnatal and long-term damage in cerebellar GCPs at age P7 after hyperoxia and also after recovery in room air thereafter until P11 and P30...
May 25, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28386343/signaling-by-tgf-betas-in-tubule-cultures-of-adult-rat-testis
#5
Kai-Hui Chan, Sebastian P Galuska, Pradeep Kumar Kudipudi, Mohammad Assad Riaz, Kate L Loveland, Lutz Konrad
Although signal transduction of transforming growth factor-betas (TGF-βs) is well characterized in individual cell types, data about TGF-β signaling in a cellular context is still scarce. In this study, we used ex vivo tubule cultures from adult rat testis to investigate TGF-β signaling. We show for the first time in testicular tubules, that TGF-βs also signal via the BMP type I receptors, with ALK2 used by TGF-β1 and ALK3 and ALK6 by TGF-β2. This signal transduction is mediated via Smad3 as well as via Smad1...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28168441/late-effect-of-developmental-exposure-to-3-3-iminodipropionitrile-on-neurogenesis-in-the-hippocampal-dentate-gyrus-of-mice
#6
Yasuko Hasegawa-Baba, Takeshi Tanaka, Yousuke Watanabe, Liyun Wang, Megu Itahashi, Toshinori Yoshida, Makoto Shibutani
The effects of developmental exposure to 3,3'-iminodipropionitrile (IDPN), a neurotoxicant that causes proximal axonopathy, on mouse hippocampal neurogenesis was examined. Pregnant mice were exposed to IDPN at 0, 600, or 1200 ppm in their drinking water from gestational day 6 to postnatal day (PND) 21. On PND 21, male offspring showed increased postmitotic neuron-specific NeuN-immunoreactive((+)) granule cell numbers in the dentate subgranular zone (SGZ) and granule cell layer (GCL) and decreased glutamate receptor gene Grin2d levels in the dentate gyrus at 1200 ppm...
February 6, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28078709/expression-of-transcription-factors-divide-retinal-ganglion-cells-into-distinct-classes
#7
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
#8
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
#9
REVIEW
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
#10
REVIEW
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
#11
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
#12
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
#13
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...
June 1, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/27581449/a-novel-and-multivalent-role-of-pax6-in-cerebellar-development
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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