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Long Yan, Yue Li, Zixiao Shi, Xiaoyin Lu, Jiao Ma, Baoyang Hu, Jianwei Jiao, Hongmei Wang
The zinc finger E-box binding transcription factor Zeb1 plays a pivotal role in the epithelial-mesenchymal transition (EMT). Numerous studies have focused on the molecular mechanisms by which Zeb1 contributes to this process. However, the functions of Zeb1 beyond EMT remain largely elusive. Using a transdifferentiation system to convert mouse embryonic fibroblasts (MEFs) into functional neurons via the neuronal transcription factors Achaete-scute family bHLH transcription factor1 (Ascl1), POU class 3 homeobox 2 (POU3F2/Brn2) and Neurogenin 2 (Neurog2, Ngn2) (ABN), we found that Zeb1 was up-regulated during the early stages of transdifferentiation...
May 12, 2017: Journal of Biological Chemistry
Parisa Farzanehfar, Malcolm K Horne, Tim D Aumann
Generation of new dopamine (DA) neurons in the adult midbrain is a controversial issue in development of better treatments for Parkinson's disease (PD). Previous research suggests Nestin-expressing neural precursor cells (NPCs) have a propensity to differentiate into neurons here, including DA neurons. In the present study we sought confirmation of this by studying gene expression in single Nestin-expressing cells and their progeny/ontogeny within the adult mouse midbrain. Cells were identified by administering a pulse of Tamoxifen to adult Nestin-CreER(T2)×R26eYFP transgenic mice...
March 29, 2017: Neuroscience Letters
Mitsunori D Arai, Bo Zhan, Atsuko Maruyama, Akiko Matsui-Harada, Kazuhiro Horinouchi, Shoji Komai
Neural stem cell (NSC) transplantation is a promising therapeutic modality for various nervous-system disorders; however, poor survival and differentiation of the transplanted NSCs limit their therapeutic efficacy. This study elucidated the effect of additive rehabilitative therapy with enriched environment (EE) and of achaete-scute homolog 1 (Mash1) and neurogenin2 (Ngn2) transduction on the fate of NSCs (P28-P35) transplanted into the primary somatosensory cortex (PSC) of mice. NSCs transplanted into the PSC differentiated into neurons and astrocytes and exhibited typical excitatory and synaptic response in mice housed in standard cages or in the EE...
February 15, 2017: Journal of the Neurological Sciences
Kohei Homma, Sumiko Usui, Makoto Kaneda
Fluorescent reporter gene knock-in induced pluripotent stem cell (iPSC) lines have been used to evaluate the efficiency of differentiation into specific cell lineages. Here, we report a knock-in strategy for the generation of human iPSC reporter lines in which a 2A peptide sequence and a red fluorescent protein (E2-Crimson) gene were inserted at the termination codon of the cone-rod homeobox (Crx) gene, a photoreceptor-specific transcriptional factor gene. The knock-in iPSC lines were differentiated into fluorescence-expressing cells in 3D retinal differentiation culture, and the fluorescent cells also expressed Crx specifically in the nucleus...
March 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
Silvia Velasco, Mahmoud M Ibrahim, Akshay Kakumanu, Görkem Garipler, Begüm Aydin, Mohamed Ahmed Al-Sayegh, Antje Hirsekorn, Farah Abdul-Rahman, Rahul Satija, Uwe Ohler, Shaun Mahony, Esteban O Mazzoni
Direct cell programming via overexpression of transcription factors (TFs) aims to control cell fate with the degree of precision needed for clinical applications. However, the regulatory steps involved in successful terminal cell fate programming remain obscure. We have investigated the underlying mechanisms by looking at gene expression, chromatin states, and TF binding during the uniquely efficient Ngn2, Isl1, and Lhx3 motor neuron programming pathway. Our analysis reveals a highly dynamic process in which Ngn2 and the Isl1/Lhx3 pair initially engage distinct regulatory regions...
February 2, 2017: Cell Stem Cell
J Xu, B J Hartley, P Kurup, A Phillips, A Topol, M Xu, C Ononenyi, E Foscue, S-M Ho, T D Baguley, N Carty, C S Barros, U Müller, S Gupta, P Gochman, J Rapoport, J A Ellman, C Pittenger, B Aronow, A C Nairn, M W Nestor, P J Lombroso, K J Brennand
The brain-specific tyrosine phosphatase, STEP (STriatal-Enriched protein tyrosine Phosphatase) is an important regulator of synaptic function. STEP normally opposes synaptic strengthening by increasing N-methyl D-aspartate glutamate receptor (NMDAR) internalization through dephosphorylation of GluN2B and inactivation of the kinases extracellular signal-regulated kinase 1/2 and Fyn. Here we show that STEP61 is elevated in the cortex in the Nrg1(+/-) knockout mouse model of schizophrenia (SZ). Genetic reduction or pharmacological inhibition of STEP prevents the loss of NMDARs from synaptic membranes and reverses behavioral deficits in Nrg1(+/-) mice...
October 18, 2016: Molecular Psychiatry
Kwaku Dad Abu-Bonsrah, Dongcheng Zhang, Donald F Newgreen
Chickens are an invaluable model for studying human diseases, physiology and especially development, but have lagged in genetic applications. With the advent of Programmable Engineered Nucleases, genetic manipulation has become efficient, specific and rapid. Here, we show that the CRISPR/Cas9 system can precisely edit the chicken genome. We generated HIRA, TYRP1, DICER, MBD3, EZH2, and 6 other gene knockouts in two chicken cell lines using the CRISPR/Cas9 system, with no off-target effects detected. We also showed that very large deletions (>75 kb) could be achieved...
October 3, 2016: Scientific Reports
Gabriel Rusanescu, Jianren Mao
Unilateral peripheral nerve chronic constriction injury (CCI) has been widely used as a research model of human neuropathic pain. Recently, CCI has been shown to induce spinal cord adult neurogenesis, which may contribute to the chronic increase in nociceptive sensitivity. Here, we show that CCI also induces rapid and profound asymmetrical anatomical rearrangements in the adult rodent cerebellum and pons. This remodelling occurs throughout the hindbrain, and in addition to regions involved in pain processing, also affects other sensory modalities...
February 2017: Journal of Cellular and Molecular Medicine
Micheli M Pillat, Claudiana Lameu, Cleber A Trujillo, Talita Glaser, Angélica R Cappellari, Priscilla D Negraes, Ana M O Battastini, Telma T Schwindt, Alysson R Muotri, Henning Ulrich
During brain development, cells proliferate, migrate and differentiate in highly accurate patterns. In this context, published results indicate that bradykinin functions in neural fate determination, favoring neurogenesis and migration. However, mechanisms underlying bradykinin function are yet to be explored. Our findings indicate a previously unidentified role for bradykinin action in inducing neuron-generating division in vitro and in vivo, given that bradykinin lengthened the G1-phase of the neural progenitor cells (NPC) cycle and increased TIS21 (also known as PC3 and BTG2) expression in hippocampus from newborn mice...
September 15, 2016: Journal of Cell Science
Jia Yu, Xueting Li, Junwei Yang, Yanping Wu, Baixiang Li
BACKGROUND Simazine is a triazine herbicide used worldwide in both agricultural and non-agricultural fields that is frequently detected in surface water and groundwater. Due to its widespread use, an increasing amount of research has focused on the potentially serious environmental and health risks. MATERIAL AND METHODS We used Western blotting and real-time quantitative PCR to analyze the effects of simazine on dopamine neuronal development-related factors in MN9D dopaminergic cells. RESULTS The expression of tyrosine hydroxylase (TH) mRNA was significantly increased after treatment with 300 and 600 μmol L-1 simazine after 24 and 48 h...
August 11, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
G Christopher Tan, Esteban O Mazzoni, Hynek Wichterle
The motor neuron progenitor domain in the ventral spinal cord gives rise to multiple subtypes of motor neurons and glial cells. Here, we examine whether progenitors found in this domain are multipotent and which signals contribute to their cell-type-specific differentiation. Using an in vitro neural differentiation model, we demonstrate that motor neuron progenitor differentiation is iteratively controlled by Notch signaling. First, Notch controls the timing of motor neuron genesis by repressing Neurogenin 2 (Ngn2) and maintaining Olig2-positive progenitors in a proliferative state...
July 26, 2016: Cell Reports
Zhi-Hua Liu, Ying Xie, Jun Tang, Chun-Feng Liu
PURPOSE: To explore the feasibility of the application of (99m)Tc-DTPA-Nateglinide as a nuclear medicine imaging agent for evaluating pancreatic B cell function. METHODS: (1) Distribution of the experiment: Forty-two mice were selected and divided into seven groups. Each mice was injected with 3.7 MBq (100 μCi) of (99m)Tc-DTPA-NGN2 from the vena caudalis and was sacrificed by bloodletting at five minutes, 15 minutes, 30 minutes, one hour, two hours, four hours and six hours, respectively...
2016: American Journal of Translational Research
HongNa Yang, Jing Wang, Feng Wang, XiaoDun Liu, Heng Chen, WeiMing Duan, TingYu Qu
Transplantation of dopaminergic (DA) neurons is considered to be the most promising therapeutic strategy for replacing degenerated dopamine cells in the midbrain of Parkinson's disease (PD), thereby restoring normal neural circuit function and slow clinical progression of the disease. Human neural stem cells (hNSCs) derived from fetal forebrain are thought to be the important cell sources for producing DA neurons because of their multipotency for differentiation and long-term expansion property in cultures...
2016: Frontiers in Neural Circuits
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
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...
December 2016: Developmental Neurobiology
Xinxin Wang, Shanshan Ma, Nan Meng, Ning Yao, Kun Zhang, Qinghua Li, Yanting Zhang, Qu Xing, Kang Han, Jishi Song, Bo Yang, Fangxia Guan
Resveratrol (RES) plays a critical role in the fate of cells and longevity of animals via activation of the sirtuins1 (SIRT1) gene. In the present study, we intend to investigate whether RES could promote the self-renewal and neural-lineage differentiation in human umbilical cord derived MSCs (hUC-MSCs) in vitro at concentrations ranging from 0.1 to 10 μM, and whether it exerts the effects by modulating the SIRT1 signaling. Herein, we demonstrated that RES at the concentrations of 0.1, 1 and 2.5 μM could promote cell viability and proliferation, mitigate senescence and induce expression of SIRT1 and Proliferating Cell Nuclear Antigen (PCNA) while inhibit the expression of p53 and p16...
May 31, 2016: Molecules and Cells
Pin Chen, Qing Yan, Songtao Wang, Cunzu Wang, Peng Zhao
Alzheimer's disease (AD) is an irreversible and progressive neurodegenerative disorder with observable memory impairment. The present study was performed to evaluate the beneficial effects of lentiviral vector-mediated overexpression of a combination of three transcription regulators, ABN (Ascl1, Brn2 and Ngn2), on learning and memory loss in a mouse model of AD. The AD model was established by injecting Aβ1-42 bilaterally into the mouse hippocampus. Lentiviral ABN was delivered bilaterally into the hippocampus of mice...
August 1, 2016: Gene
Fatima Memic, Viktoria Knoflach, Rebecca Sadler, Gunilla Tegerstedt, Erik Sundström, Francois Guillemot, Vassilis Pachnis, Ulrika Marklund
UNLABELLED: The enteric nervous system (ENS) is organized into neural circuits within the gastrointestinal wall where it controls the peristaltic movements, secretion, and blood flow. Although proper gut function relies on the complex neuronal composition of the ENS, little is known about the transcriptional networks that regulate the diversification into different classes of enteric neurons and glia during development. Here we redefine the role of Ascl1 (Mash1), one of the few regulatory transcription factors described during ENS development...
April 13, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Niurka Trujillo-Paredes, Concepción Valencia, Gilda Guerrero-Flores, Dulce-María Arzate, José-Manuel Baizabal, Magdalena Guerra-Crespo, Ayari Fuentes-Hernández, Iván Zea-Armenta, Luis Covarrubias
Notch signalling is a well-established pathway that regulates neurogenesis. However, little is known about the role of Notch signalling in specific neuronal differentiation. Using Dll1 null mice, we found that Notch signalling has no function in the specification of mesencephalic dopaminergic neural precursor cells (NPCs), but plays an important role in regulating their expansion and differentiation into neurons. Premature neuronal differentiation was observed in mesencephalons of Dll1-deficient mice or after treatment with a Notch signalling inhibitor...
2016: Biology Open
Hirokazu Hashimoto, Yugo Ishino, Wen Jiang, Takeshi Yoshimura, Yoshiko Takeda-Uchimura, Kenji Uchimura, Kenji Kadomatsu, Kazuhiro Ikenaka
Keratan sulfate (KS) is a sulfated glycosaminoglycan and has been shown to bind to sonic hedgehog (Shh), which act as a morphogen to regulate the embryonic spinal cord development. We found highly sulfated KS was present in the floor plate (including lateral floor plate) and the notochord . This expression colocalized with Shh expression. To understand the roles of KS, we analyzed the embryonic spinal cord of GlcNAc6ST-1, KS chain synthesizing enzyme, knock-out (KO) mice. At E12.5, the pMN domain, whose formation is controlled by Shh signaling, became shifted ventrally in GlcNAc6ST-1 KO mice...
February 2016: Neurochemical Research
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