Wls-mediated Wnts differentially regulate distal limb patterning and tissue morphogenesis

Xuming Zhu, Huang Zhu, Lingling Zhang, Sixia Huang, Jingjing Cao, Gang Ma, Guoying Feng, Lin He, Yingzi Yang, Xizhi Guo

Research output: Contribution to journalArticlepeer-review

56 Scopus citations


Wnt proteins are diffusible morphogens that play multiple roles during vertebrate limb development. However, the complexity of Wnt signaling cascades and their overlapping expression prevent us from dissecting their function in limb patterning and tissue morphogenesis. Depletion of the . Wntless (. Wls) gene, which is required for the secretion of various Wnts, makes it possible to genetically dissect the overall effect of Wnts in limb development. In this study, the . Wls gene was conditionally depleted in limb mesenchyme and ectoderm. The loss of mesenchymal . Wls prevented the differentiation of distal mesenchyme and arrested limb outgrowth, most likely by affecting Wnt5a function. Meanwhile, the deletion of ectodermal . Wls resulted in agenesis of distal limb tissue and premature regression of the distal mesenchyme. These observations suggested that Wnts from the two germ layers differentially regulate the pool of undifferentiated distal limb mesenchyme cells. Cellular behavior analysis revealed that ectodermal Wnts sustain mesenchymal cell proliferation and survival in a manner distinct from Fgf. Ectodermal Wnts were also shown for the first time to be essential for distal tendon/ligament induction, myoblast migration and dermis formation in the limb. These findings provide a comprehensive view of the role of Wnts in limb patterning and tissue morphogenesis.

Original languageEnglish
Pages (from-to)328-338
Number of pages11
JournalDevelopmental Biology
Issue number2
StatePublished - 15 May 2012
Externally publishedYes


  • Limb
  • Patterning
  • Tendon/ligament
  • Tissue morphogenesis
  • Wnt
  • Wntless


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