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Hes6 acts in a positive feedback loop with the neurogenins to promote neuronal differentiation

Koyano-Nakagawa, Naoko and Kim, Jaesang and Anderson­, David J. and Kintner, Chris (2000) Hes6 acts in a positive feedback loop with the neurogenins to promote neuronal differentiation. Development, 127 (19). pp. 4203-4216. ISSN 0950-1991.

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During the development of the vertebrate nervous system, neurogenesis is promoted by proneural bHLH proteins such as the neurogenins, which act as potent transcriptional activators of neuronal differentiation genes. The pattern by which these proteins promote neuronal differentiation is thought to be governed by inhibitors, including a class of transcriptional repressors called the WRPW-bHLH proteins, which are similar to Drosophila proteins encoded by hairy and genes in the enhancer of split complex (E-(SPL)-C). Here, we describe the isolation and characterization of Hes6, which encodes a novel WRPW-bHLH protein expressed during neurogenesis in mouse and Xenopus embryos. We show that Hes6 expression follows that of neurogenins but precedes that of the neuronal differentiation genes. We provide several lines of evidence to show that Hes6 expression occurs in developing neurons and is induced by the proneural bHLH proteins but not by the Notch pathway. When ectopically expressed in Xenopus embryos, Hes6 promotes neurogenesis. The properties of Hes6 distinguish it from other members of the WRPW-bHLH family in vertebrates, and suggest that it acts in a positive-feedback loop with the proneural bHLH proteins to promote neuronal differentiation.

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Anderson­, David J.0000-0001-6175-3872
Additional Information:Copyright © 2000 by Company of Biologists. Accepted 18 July; published on WWW 7 September 2000. The authors thank Dr Elise Lamar for helpful and careful comments on the manuscript. We thank P. Mombaerts for the tau-lacZ plasmid, J. Lee for the NeuroD probe, A. Ruiz i Altaba for Xenopus Zic2 probe, J. Gurdon for Xenopus E12 plasmid, K. Kuhlbrodt and M. Wegner for the Sox10 probe, Shirley Pease for performing blastocyst injections, and the staff of the Caltech Transgenic Facility for mouse care. We thank Dr Wui-Chuong Jen for the generation of the hairy2A and the hairy2A-Gal4 expression constructs, and Dr H.U. Wang for early contributions to the isolation of Hes6. D.J.A. is an investigator of the Howard Hughes Medical Institute. The work reported here was supported in part by the Human Frontier Science Program, the Uehara Memorial Foundation (N.K.-N.), and by a grant from NIH (C.K.).
Funding AgencyGrant Number
Howard Hughes Medical InstituteUNSPECIFIED
Human Frontier Science ProgramUNSPECIFIED
Uehara Memorial FoundationUNSPECIFIED
National Institutes of HealthUNSPECIFIED
Subject Keywords:Neurogenins, Mouse, Xenopus, Hes6, Differentiation
Issue or Number:19
Record Number:CaltechAUTHORS:KOYdev00
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:11638
Deposited By: Archive Administrator
Deposited On:15 Sep 2008 05:03
Last Modified:09 Mar 2020 13:18

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