Get access

Wnts and wing: Wnt signaling in vertebrate limb development and musculoskeletal morphogenesis


  • Yingzi Yang

    Corresponding author
    1. Genetic Disease Research Branch, National Human Genome Research Institute, Bethesda, Maryland
    • Genetic Disease Research Branch, National Human Genome Research Institute, Building 49, Room 4A68, 49 Convent Drive, MSC 4472, Bethesda, MD 20892
    Search for more papers by this author

  • This article is a US Government work and, as such, is in the public domain in the United States of America.


In the past twenty years, secreted signaling molecules of the Wnt family have been found to play a central role in controlling embryonic development from hydra to human. In the developing vertebrate limb, Wnt signaling is required for limb bud initiation, early limb patterning (which is governed by several well-characterized signaling centers), and, finally, late limb morphogenesis events. Wnt ligands are unique, in that they can activate several different receptor-mediated signal transduction pathways. The most extensively studied Wnt pathway is the canonical Wnt pathway, which controls gene expression by stabilizing β-catenin in regulating a diverse array of biological processes. Recently, more attention has been given to the noncanonical Wnt pathway, which is β-catenin–independent. The noncanonical Wnt pathway signals through activating Ca2+ flux, JNK activation, and both small and heterotrimeric G proteins, to induce changes in gene expression, cell adhesion, migration, and polarity. Abnormal Wnt signaling leads to developmental defects and human diseases affecting either tissue development or homeostasis. Further understanding of the biological function and signaling mechanism of Wnt signaling is essential for the development of novel preventive and therapeutic approaches of human diseases. This review provides a critical perspective on how Wnt signaling regulates different developmental processes. As Wnt signaling in tumor formation has been reviewed extensively elsewhere, this part is not included in the review of the clinical significance of Wnt signaling. Birth Defects Research (Part C) 69:305–317, 2003. Published 2003 Wiley-Liss, Inc.

Get access to the full text of this article