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Constitutive expression of the neuron-restrictive silencer factor (NRSF)/REST in differentiating neurons disrupts neuronal gene expression and causes axon pathfinding errors in vivo

Paquette, Alice J. and Perez, Sharon E. and Anderson, David J. (2000) Constitutive expression of the neuron-restrictive silencer factor (NRSF)/REST in differentiating neurons disrupts neuronal gene expression and causes axon pathfinding errors in vivo. Proceedings of the National Academy of Sciences of the United States of America, 97 (22). pp. 12318-12323. ISSN 0027-8424. PMCID PMC17339. https://resolver.caltech.edu/CaltechAUTHORS:PAQpnas00

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Abstract

The neuron-restrictive silencer factor (NRSF; also known as REST for repressor element-1 silencing transcription factor) is a transcriptional repressor of multiple neuronal genes, but little is known about its function in vivo. NRSF is normally down-regulated upon neuronal differentiation. Constitutive expression of NRSF in the developing spinal cord of chicken embryos caused repression of two endogenous target genes, N-tubulin and Ng-CAM, but did not prevent overt neurogenesis. Nevertheless, commissural neurons that differentiated while constitutively expressing NRSF showed a significantly increased frequency of axon guidance errors. These data suggest that down-regulation of NRSF is necessary for the proper development of at least some classes of neurons in vivo.


Item Type:Article
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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC17339/PubMed CentralArticle
Additional Information:© 2000 by the National Academy of Sciences. Communicated by Masakazu Konishi, California Institute of Technology, Pasadena, CA, August 4, 2000 (received for review June 20, 2000). We thank the Developmental Studies Hybridoma Bank for monoclonal antibodies, Jim Haseloff and Emma Dormand for IRES-tauGFP cassettes, Hieu Phan for scoring sections, Gabe Miller and Pat White for help with statistical analysis and preparation of figures, and Kai Zinn and Jane Dodd for critical comments on the manuscript. This work was supported by National Institutes of Health Grant NS23476. D.J.A. is an investigator of the Howard Hughes Medical Institute. The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Funders:
Funding AgencyGrant Number
NIHNS23476
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Subject Keywords:CELL-ADHESION MOLECULE; ACETYLCHOLINE-RECEPTOR GENE; SODIUM-CHANNEL GENE; HELIX FACTOR HES-1; RAT SPINAL-CORD; NERVOUS-SYSTEM; GROWTH CONES; IN-VIVO; TRANSCRIPTIONAL REGULATION; COMMISSURAL NEURONS
Issue or Number:22
PubMed Central ID:PMC17339
Record Number:CaltechAUTHORS:PAQpnas00
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:PAQpnas00
Alternative URL:http://dx.doi.org/10.1073/pnas.97.22.12318
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:10923
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:19 Jun 2008
Last Modified:03 Oct 2019 00:14

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