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Wnt2/2b and beta-Catenin Signaling Are Necessary and Sufficient to Specify Lung Progenitors in the Foregut

  1. Author:
    Goss, A. M.
    Tian, Y.
    Tsukiyama, T.
    Cohen, E. D.
    Zhou, D.
    Lu, M. M.
    Yamaguchi, T. P.
    Morrisey, E. E.

  2. Author Address

    Goss, Ashley M.; Tian, Ying, Cohen, Ethan David, Zhou, Diane, Lu, Min Min, Morrisey, Edward E.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Goss, Ashley M.; Morrisey, Edward E.] Univ Penn, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA. [Tian, Ying, Cohen, Ethan David, Zhou, Diane, Lu, Min Min, Morrisey, Edward E.] Univ Penn, Cardiovasc Inst, Philadelphia, PA 19104 USA. [Tsukiyama, Tadasuke, Yamaguchi, Terry P.] NCI, Canc & Dev Biol Lab, NIH, Frederick, MD 21702 USA. [Morrisey, Edward E.] Univ Penn, Inst Regenerat Med, Philadelphia, PA 19104 USA.
    1. Year: 2009
  2. Journal: Developmental Cell
    1. 17
    2. 2
    3. Pages: 290-298
  4. Type of Article: Article
  1. Abstract:

    Patterning of the primitive foregut promotes appropriate organ specification along its anterior-posterior axis. However, the molecular pathways specifying foregut endoderm progenitors are poorly understood. We show here that Wnt2/2b signaling is required to specify lung endoderm progenitors within the anterior foregut. Embryos lacking Wnt2/2b expression exhibit complete lung agenesis and do not express Nkx2.1, the earliest marker of the lung endoderm. In contrast, other foregut endoderm-derived organs, including the thyroid, liver, and pancreas, are correctly specified. The phenotype observed is recapitulated by an endoderm-restricted deletion of beta-catenin, demonstrating that Wnt2/2b signaling through the canonical Writ pathway is required to specify lung endoderm progenitors within the foregut. Moreover, activation of canonical Wnt/beta-catenin signaling results in the reprogramming of esophagus and stomach endoderm to a lung endoderm progenitor fate. Together, these data reveal that canonical Wnt2/2b signaling is required for the specification of lung endoderm progenitors in the developing foregut.

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  2. DOI: 10.1016/j.devcel.2009.06.005
  3. PMID: 19686689

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