Expression of Wnt9b and activation of canonical Wnt signaling during midfacial morphogenesis in mice

Authors

  • Yu Lan,

    1. Center for Oral Biology and Department of Biomedical Genetics, University of Rochester School of Medicine and Dentistry, Rochester, New York
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    • Y. Lan and R. C. Ryan contributed equally to this work.

  • Rosemary C. Ryan,

    1. Departments of Biology, University of Rochester, Rochester, New York
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    • Y. Lan and R. C. Ryan contributed equally to this work.

  • Zunyi Zhang,

    1. Center for Oral Biology and Department of Biomedical Genetics, University of Rochester School of Medicine and Dentistry, Rochester, New York
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  • Steven A. Bullard,

    1. Department of Orthodontics and Dows Institute for Dental Research, University of Iowa School of Dentistry, Iowa City, Iowa
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  • Jeffrey O. Bush,

    1. Center for Oral Biology and Department of Biomedical Genetics, University of Rochester School of Medicine and Dentistry, Rochester, New York
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  • Kathleen M. Maltby,

    1. Center for Oral Biology and Department of Biomedical Genetics, University of Rochester School of Medicine and Dentistry, Rochester, New York
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  • Andrew C. Lidral,

    1. Department of Orthodontics and Dows Institute for Dental Research, University of Iowa School of Dentistry, Iowa City, Iowa
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  • Rulang Jiang

    Corresponding author
    1. Center for Oral Biology and Department of Biomedical Genetics, University of Rochester School of Medicine and Dentistry, Rochester, New York
    2. Departments of Biology, University of Rochester, Rochester, New York
    • Center for Oral Biology, University of Rochester Medical Center, 601 Elmwood Avenue, Box 611, Rochester, NY 14642
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Abstract

Cleft lip with or without cleft palate (CLP) is the most common craniofacial birth defect in humans. Recently, mutations in the WNT3 and Wnt9b genes, encoding two members of the Wnt family of signaling molecules, were found associated with CLP in human and mice, respectively. To investigate whether Wnt3 and Wnt9b directly regulate facial development, we analyzed their developmental expression patterns and found that both Wnt3 and Wnt9b are expressed in the facial ectoderm at critical stages of midfacial morphogenesis during mouse embryogenesis. Whereas Wnt3 mRNA is mainly expressed in the maxillary and medial nasal ectoderm, Wnt9b mRNA is expressed in maxillary, medial nasal, and lateral nasal ectoderm. During lip fusion, Wnt9b, but not Wnt3, is expressed in the epithelial seam between the fusing medial and lateral nasal processes. Furthermore, we found that expression of TOPGAL, a transgenic reporter of activation of canonical Wnt signaling pathway, is specifically activated in the distal regions of the medial nasal, lateral nasal, and maxillary processes prior to lip fusion. During lip fusion, the epithelial seam between the medial and lateral nasal processes as well as the facial mesenchyme directly beneath the fusing epithelia strongly expresses TOPGAL. These data, together with the CLP lip phenotype in WNT3−/− humans and Wnt9b−/− mutant mice, indicate that Wnt3 and Wnt9b signal through the canonical Wnt signaling pathway to regulate midfacial development and lip fusion. Developmental Dynamics, 2006. © 2006 Wiley-Liss, Inc.

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