title: Wls-mediated Wnts differentially regulate distal limb patterning and tissue morphogenesis.
abstract: 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.
authors.affiliation: Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, China.
authors.forename: Xuming
authors.initials: X
authors.lastname: Zhu
authors.forename: Huang
authors.initials: H
authors.lastname: Zhu
authors.forename: Lingling
authors.initials: L
authors.lastname: Zhang
authors.forename: Sixia
authors.initials: S
authors.lastname: Huang
authors.forename: Jingjing
authors.initials: J
authors.lastname: Cao
authors.forename: Gang
authors.initials: G
authors.lastname: Ma
authors.forename: Guoying
authors.initials: G
authors.lastname: Feng
authors.forename: Lin
authors.initials: L
authors.lastname: He
authors.forename: Yingzi
authors.initials: Y
authors.lastname: Yang
authors.forename: Xizhi
authors.initials: X
authors.lastname: Guo
mesh_terms: D000818:Animals; D019521:Body Patterning; D002454:Cell Differentiation; D002642:Chick Embryo; D004475:Ectoderm / Q000166:cytology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D035002:Lower Extremity / Q000196:embryology*; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D043562:Receptors, G-Protein-Coupled; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: C545200:Gpr177 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D043562:Receptors, G-Protein-Coupled; D051153:Wnt Proteins; D051176:beta Catenin