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The organizer factors Chordin and Noggin are required for mouse forebrain development

Nature volume 403, pages 658–661 (2000)Cite this article

Abstract

In mice, there is evidence suggesting that the development of head and trunk structures is organized by distinctly separated cell populations1,2. The head organizer is located in the anterior visceral endoderm (AVE) and the trunk organizer in the node and anterior primitive streak. In amphibians, Spemann's organizer, which is homologous to the node, partially overlaps with anterior endoderm cells expressing homologues of the AVE markers cerberus, Hex and Hesx1 (refs 3,4,5,6). For mice, this raises the question of whether the AVE and node are independent of each other, as suggested by their anatomical separation, or functionally interdependent as is the case in amphibians3,4,5. Chordin and Noggin are secreted bone morphogenetic protein (BMP) antagonists7,8 expressed in the mouse node, but not in the AVE. Here we show that mice double-homozygous mutants that are for chordin and noggin display severe defects in the development of the prosencephalon. The results show that BMP antagonists in the node and its derivatives are required for head development.

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Figure 1: Expression of chordin and noggin in the node and phenotype of double mutants.
Figure 2: Loss of forebrain in chordin;noggin double mutants.
Figure 3: Molecular marker analyses of double chordin;noggin mutants during early development.

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Acknowledgements

We thank R. Beddington, G. Oliver, D. Wilkinson and A. Joyner for gifts of plasmids, K. Woo, C. De Robertis, B. Yoon and A. Burnett for help with genotyping, and K. Lyons, G. Weinmaster, E. Delot and members of our laboratories for comments on the manuscript. This work was supported by the HHMI, NIH, MRC Canada, Whitehead Foundation and the Norman Sprague Chair.

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Authors and Affiliations

  1. Howard Hughes Medical Institute and Department of Biological Chemistry, University of California, Los Angeles, 90095-1662, California, USA

    Daniel Bachiller, C. Kemp, J. A. Belo & E. M. De Robertis

  2. Department of Cell Biology, Duke University Medical Center, Durham, 27710 , North Carolina, USA

    John Klingensmith, R. M. Anderson & S. R. May

  3. Department of Molecular and Cell Biology, Harvard University, Cambridge, 02138, Massachusetts , USA

    J. A. McMahon & A. P. McMahon

  4. Department of Molecular and Cell Biology, University of California, Berkeley, 94720-3204, California , USA

    R. M. Harland

  5. Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto , M5G 1X5, Canada

    J. Rossant

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Bachiller, D., Klingensmith, ., Kemp, C. et al. The organizer factors Chordin and Noggin are required for mouse forebrain development. Nature 403, 658–661 (2000). https://doi.org/10.1038/35001072

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