Hes1 and Hes3 regulate maintenance of the isthmic organizer and development of the mid/hindbrain

Hes1 and Hes3 regulate maintenance of the isthmic organizer and development of the mid/hindbrain The isthmic organizer, which is located at the midbrain–hindbrain boundary, plays an essential role in development of the midbrain and anterior hindbrain. It has been shown that homeobox genes regulate establishment of the isthmic organizer, but the mechanism by which the organizer is maintained is not well understood. Here, we found that, in mice doubly mutant for the basic helix–loop–helix genes Hes1 and Hes3, the midbrain and anterior hindbrain structures are missing without any significant cell death. In these mutants, the isthmic organizer cells prematurely differentiate into neurons and terminate expression of secreting molecules such as Fgf8 and Wnt1 and the paired box genes Pax2/5, all of which are essential for the isthmic organizer function. These results indicate that Hes1 and Hes3 prevent premature differentiation and maintain the organizer activity of the isthmic cells, thereby regulating the development of the midbrain and anterior hindbrain. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The EMBO Journal Wiley

Hes1 and Hes3 regulate maintenance of the isthmic organizer and development of the mid/hindbrain

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Publisher
Wiley
Copyright
Copyright © 2013 Wiley Periodicals, Inc
ISSN
0261-4189
eISSN
1460-2075
DOI
10.1093/emboj/20.16.4454
Publisher site
See Article on Publisher Site

Abstract

The isthmic organizer, which is located at the midbrain–hindbrain boundary, plays an essential role in development of the midbrain and anterior hindbrain. It has been shown that homeobox genes regulate establishment of the isthmic organizer, but the mechanism by which the organizer is maintained is not well understood. Here, we found that, in mice doubly mutant for the basic helix–loop–helix genes Hes1 and Hes3, the midbrain and anterior hindbrain structures are missing without any significant cell death. In these mutants, the isthmic organizer cells prematurely differentiate into neurons and terminate expression of secreting molecules such as Fgf8 and Wnt1 and the paired box genes Pax2/5, all of which are essential for the isthmic organizer function. These results indicate that Hes1 and Hes3 prevent premature differentiation and maintain the organizer activity of the isthmic cells, thereby regulating the development of the midbrain and anterior hindbrain.

Journal

The EMBO JournalWiley

Published: Mar 15, 2002

Keywords: ; ; ; ;

References

  • Otx2, Gbx2 and Fgf8 interact to position and maintain a mid–hindbrain organizer
    Joyner, AL; Liu, A; Millet, S
  • Hes1 and Hes5 as Notch effectors in mammalian neuronal differentiation
    Ohtsuka, T; Ishibashi, M; Gradwohl, G; Nakanishi, S; Guillemot, F; Kageyama, R
  • The midbrain–hindbrain boundary organizer
    Rhinn, M; Brand, M
  • Mammalian achaete‐scute and atonal homologs regulate neuronal versus glial fate determination in the central nervous system
    Tomita, K; Moriyoshi, K; Nakanishi, S; Guillemot, F; Kageyama, R

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