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Published October 24, 2000 | Published
Journal Article Open

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


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.

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.

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