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Distinct regulators control the expression of the mid-hindbrain organizer signal FGF8

Nature Neuroscience volume 4, pages 1175–1181 (2001)Cite this article

Abstract

Local expression of FGF8 at the mid/hindbrain boundary (MHB) governs the development of multiple neurons and support cells. Here we show that the paired-domain protein Pax2 is necessary and sufficient for the induction of FGF8 in part by regulating the expression of Pax5&8. A network of transcription and secreted factors, including En1, Otx2, Gbx2, Grg4 and Wnt1&4, that is established independently of Pax2, further refines the expression domain and level of FGF8 at the MHB through opposing effects on Pax2 activity. Our results indicate that the expression of local organizing factors is controlled by combinatorial interaction between inductive and modulatory factors.

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Figure 1: Expression pattern of endogenous Otx2, Gbx2, Pax2, FGF8 and Wnt1 in the chick embryos.
Figure 2: Ectopic expression of Otx2 and Pax2 in the chick embryo.
Figure 3: Ectopic expression of Gbx2 and Pax2 in the chick embryo.
Figure 4: Absence of FGF8 expression in Pax2−/− mouse embryos.
Figure 5: Regulation and activity of Grg4, En1 and Wnt1.
Figure 6: Putative interactions between negative and positive regulators of FGF8 in the MHB.

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Acknowledgements

We thank A. Joyner for sharing unpublished results and for the chick En1 and En2 cDNAs, G. Martin, J. Rubenstein and E. Miyashita for Gbx2 mutant mice, A. Simeone for the full-length mouse and partial chick Otx2 cDNAs, A. Leutz for the full-length chick Gbx2 cDNA, G. Martin for the chick FGF8 cDNA, A. Lumsden for the chick Hoxa2 cDNA, A. McMahon for the chick Wnt1 and Wnt4 cDNAs and S. Greenwood for reading the manuscript. This research was supported in part by Boehringer Ingelheim.

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Author notes

  1. Weilan Ye and Maxime Bouchard: The first two authors contributed equally to this work

Authors and Affiliations

  1. Department of Molecular Biology, Genentech, 1 DNA Way, South San Francisco, 94080, California, USA

    Weilan Ye, Donna Stone, Xiaodong Liu & James Lee

  2. Research Institute of Molecular Pathology, Vienna Biocenter, Dr. Bohr-Gasse 7, Vienna, A-1030, Austria

    Maxime Bouchard & Meinrad Busslinger

  3. Department of Molecular Neurobiology, Institute of Development, Aging & Cancer, Tohoku University, Seiryo-machi 4-1, Aoba-ku, 980-8575, Sendai, Japan

    Harukazu Nakamura

  4. IGBMC, 1 rue Laurent Fries BP163, Illkirch, 67404, Cedex CU de Strasbourg, France

    Francis Vella & Siew-Lan Ang

  5. Rinat Neuroscience, 3155 Porter Drive, Palo Alto, 94304, California, USA

    Arnon Rosenthal

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Ye, W., Bouchard, M., Stone, D. et al. Distinct regulators control the expression of the mid-hindbrain organizer signal FGF8. Nat Neurosci 4, 1175–1181 (2001). https://doi.org/10.1038/nn761

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