Hoxa2 plays a direct role in murine palate development

Authors

  • Tara M. Smith,

    1. Laboratory of Molecular Biology, College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
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    • T.M. Smith and X. Wang contributed equally to this work.

  • Xia Wang,

    1. Laboratory of Molecular Biology, College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
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    • T.M. Smith and X. Wang contributed equally to this work.

  • Wei Zhang,

    1. Laboratory of Molecular Biology, College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
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  • William Kulyk,

    1. Department of Anatomy and Cell Biology, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
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  • Adil J. Nazarali

    Corresponding author
    1. Laboratory of Molecular Biology, College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
    • Laboratory of Molecular Biology, College of Pharmacy and Nutrition, 116 Thorvaldson Building, 110 Science Place, University of Saskatchewan, Saskatoon SK, S7N 5C9
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Abstract

The cleft palate exhibited by Hoxa2 null murine embryos has been described as being secondary to abnormalities of tongue musculature, and Hoxa2 was presumed to not play a direct role in palate development. However, we detected Hoxa2 expression in the developing palate at both the mRNA and protein levels between embryonic day (E) 12.5 and E15.5. Organ cultures of Hoxa2−/− palates maintained in the absence of the tongue showed decreased fusion rates than either Hoxa2+/− or Hoxa2+/+ palate cultures. Knocking down Hoxa2 expression with antisense retroviral constructs resulted in decreased fusion rates than corresponding controls. An overall increase in cell proliferation was observed in Hoxa2 null palates providing a potential mechanism by which Hoxa2 may be affecting palate development. Hoxa2 also repressed the expression of its downstream targets Msx1, Bmp4, Barx1, and Ptx1 within the palate. These results demonstrate the cleft palate phenotype of Hoxa2 null embryos is not solely due to abnormal tongue musculature, and indicate a direct role of Hoxa2 in regulating murine palatogenesis. Developmental Dynamics 238:2364–2373, 2009. © 2009 Wiley-Liss, Inc.

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