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A Conserved Pbx-Wnt-p63-Irf6 Regulatory Module Controls Face Morphogenesis by Promoting Epithelial Apoptosis

  1. Author:
    Ferretti, E.
    Li, B. S.
    Zewdu, R.
    Wells, V.
    Hebert, J. M.
    Karner, C.
    Anderson, M. J.
    Williams, T.
    Dixon, J.
    Dixon, M. J.
    Depew, M. J.
    Selleri, L.

  2. Author Address

    [Ferretti, E; Li, BS; Zewdu, R; Wells, V; Selleri, L] Cornell Univ, Weill Med Coll, Dept Cell & Dev Biol, New York, NY 10065 USA. [Hebert, JM] Albert Einstein Coll Med, Dept Neurosci, Bronx, NY 10461 USA. [Hebert, JM] Albert Einstein Coll Med, Dept Genet, Bronx, NY 10461 USA. [Karner, C] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA. [Karner, C] Univ Texas SW Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA. [Anderson, MJ] NCI, Genet Vertebrate Dev Sect, Frederick, MD 21701 USA. [Williams, T] Univ Colorado Denver, Dept Craniofacial Biol, Aurora, CO 80045 USA. [Williams, T] Univ Colorado Denver, Dept Cell & Dev Biol, Aurora, CO 80045 USA. [Dixon, J; Dixon, MJ] Univ Manchester, Manchester Acad Hlth Sci Ctr, Fac Med & Human Sci, Manchester M13 9PT, Lancs, England. [Depew, MJ] Kings Coll London, Dept Craniofacial Dev, London SE1 9RT, England.;Selleri, L (reprint author), Cornell Univ, Weill Med Coll, Dept Cell & Dev Biol, New York, NY 10065 USA;lis2008@med.cornell.edu
    1. Year: 2011
    2. Date: Oct
  2. Journal: Developmental Cell
    1. 21
    2. 4
    3. Pages: 627-641
  4. Type of Article: Article
  5. ISSN: 1534-5807
  1. Abstract:

    Morphogenesis of mammalian facial processes requires coordination of cellular proliferation, migration, and apoptosis to develop intricate features. Cleft lip and/or palate (CUP), the most frequent human craniofacial birth defect, can be caused by perturbation of any of these programs. Mutations of WNT, P63, and IRF6 yield CUP in humans and mice; however, how these genes are regulated remains elusive. We generated mouse lines lacking Pbx genes in cephalic ectoderm and demonstrated that they exhibit fully penetrant CUP and perturbed Wnt signaling. We also characterized a midfacial regulatory element that Pbx proteins bind to control the expression of Wnt9b-Wnt3, which in turn regulates p63. Altogether, we establish a Pbx-dependent Wnt-p63-Irf6 regulatory module in midfacial ectoderm that is conserved within mammals. Dysregulation of this network leads to localized suppression of midfacial apoptosis and CUP. Ectopic Wnt ectodermal expression in Pbx mutants rescues the clefting, opening avenues for tissue repair.

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External Sources

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  2. DOI: 10.1016/j.devcel.2011.08.005
  3. View record in Web of Science®
  4. WOS: 000296366000008

Library Notes

  1. Fiscal Year: FY2011-2012
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