HMGB factors are required for posterior digit development through integrating signaling pathway activities

Authors

  • Junji Itou,

    1. Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota
    2. Stem Cell Institute, University of Minnesota, Minneapolis, Minnesota
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    • Junji Itou, Noboru Taniguchi, and Isao Oishi contributed equally to this work.

  • Noboru Taniguchi,

    1. Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California
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    • Junji Itou, Noboru Taniguchi, and Isao Oishi contributed equally to this work.

  • Isao Oishi,

    1. Health Research Institute, National Institute of Advanced Industrial Science and Technology, Ikeda, Osaka, Japan
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    • Junji Itou, Noboru Taniguchi, and Isao Oishi contributed equally to this work.

  • Hiroko Kawakami,

    1. Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota
    2. Stem Cell Institute, University of Minnesota, Minneapolis, Minnesota
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  • Martin Lotz,

    1. Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California
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  • Yasuhiko Kawakami

    Corresponding author
    1. Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota
    2. Stem Cell Institute, University of Minnesota, Minneapolis, Minnesota
    3. Developmental Biology Center, University of Minnesota, Minneapolis, Minnesota
    • Department of Genetics, Cell Biology and Development, Stem Cell Institute, and Developmental Biology Center, University of Minnesota, Minneapolis, MN 55455
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Abstract

The chromatin factors Hmgb1 and Hmgb2 have critical roles in cellular processes, including transcription and DNA modification. To identify the function of Hmgb genes in embryonic development, we generated double mutants of Hmgb1;Hmgb2 in mice. While double null embryos arrest at E9.5, Hmgb1−/−; Hmgb2+/− embryos exhibit a loss of digit5, the most posterior digit, in the forelimb. We show that Hmgb1−/−; Hmgb2+/− forelimbs have a reduced level of Shh signaling, as well as a clear downregulation of Wnt and BMP target genes in the posterior region. Moreover, we demonstrate that hmgb1 and hmgb2 in zebrafish embryos enhance Wnt signaling in a variety of tissues, and that double knockdown embryos have reduced Wnt signaling and shh expression in pectoral fin buds. Our data show that Hmgb1 and Hmgb2 function redundantly to enhance Wnt signaling in embryos, and further suggest that integrating Wnt, Shh, and BMP signaling regulates the development of digit5 in forelimbs. Developmental Dynamics 240:1151–1162, 2011. © 2011 Wiley-Liss, Inc.

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