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.
Bibliographical noteFunding Information:
We thank Dr. Mark Lewandoski of the NIH/NCI for providing us with the Msx2-Cre mice. This work was supported by the National Major Fundamental Research 973 program of China under grant ( 2007CB947301 and 2012CB966903 ) and by grants from the National Natural Science Foundation of China ( 31171396 and 31100624 ) and Pujiang Talent ( 08PJ1407200 ).
- Tissue morphogenesis