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Islet1-mediated activation of the beta-catenin pathway is necessary for hindlimb initiation in mice

  1. Author:
    Kawakami, Y.
    Marti, M.
    Kawakami, H.
    Itou, J.
    Quach, T.
    Johnson, A.
    Sahara, S.
    O'Leary, D. D. M.
    Nakagawa, Y.
    Lewandoski, M.
    Pfaff, S.
    Evans, S. M.
    Belmonte, J. C. I.
  2. Author Address

    [Kawakami, Y; Kawakami, H; Pfaff, S; Belmonte, JCI] Salk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA. [Kawakami, Y; Kawakami, H; Itou, J; Quach, T; Johnson, A] Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN 55455 USA. [Kawakami, Y; Kawakami, H; Itou, J; Nakagawa, Y] Univ Minnesota, Stem Cell Inst, Minneapolis, MN 55455 USA. [Kawakami, Y; Nakagawa, Y] Univ Minnesota, Ctr Dev Biol, Minneapolis, MN 55455 USA. [Kawakami, Y] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN 55455 USA. [Marti, M; Belmonte, JCI] Ctr Regenerat Med Barcelona, Barcelona 08003, Spain. [Sahara, S; O'Leary, DDM] Salk Inst Biol Studies, Molecular Neurosci Lab, La Jolla, CA 92037 USA. [Nakagawa, Y] Univ Minnesota, Dept Neurosci, Minneapolis, MN 55455 USA. [Lewandoski, M] NCI, Canc & Dev Biol Lab, Frederick, MD 21702 USA. [Evans, SM] Univ Calif San Diego, Skaggs Sch Pharm, La Jolla, CA 92093 USA. [Evans, SM] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA.;Kawakami, Y (reprint author), Salk Inst Biol Studies, Gene Express Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA;kawak005@umn.edu belmonte@salk.edu
    1. Year: 2011
    2. Date: Oct
  1. Journal: Development
    1. 138
    2. 20
    3. Pages: 4465-4473
  2. Type of Article: Article
  3. ISSN: 0950-1991
  1. Abstract:

    The transcriptional basis of vertebrate limb initiation, which is a well-studied system for the initiation of organogenesis, remains elusive. Specifically, involvement of the beta-catenin pathway in limb initiation, as well as its role in hindlimb-specific transcriptional regulation, are under debate. Here, we show that the beta-catenin pathway is active in the limb-forming area in mouse embryos. Furthermore, conditional inactivation of beta-catenin as well as Islet1, a hindlimb-specific factor, in the lateral plate mesoderm results in a failure to induce hindlimb outgrowth. We further show that Islet1 is required for the nuclear accumulation of. catenin and hence for activation of the beta-catenin pathway, and that the beta-catenin pathway maintains Islet1 expression. These two factors influence each other and function upstream of active proliferation of hindlimb progenitors in the lateral plate mesoderm and the expression of a common factor, Fgf10. Our data demonstrate that Islet1 and beta-catenin regulate outgrowth and Fgf10-Fgf8 feedback loop formation during vertebrate hindlimb initiation. Our study identifies Islet1 as a hindlimb-specific transcriptional regulator of initiation, and clarifies the controversy regarding the requirement of beta-catenin for limb initiation.

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External Sources

  1. DOI: 10.1242/dev.065359
  2. WOS: 000295085600014

Library Notes

  1. Fiscal Year: FY2011-2012
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