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Wnt regulation of limb mesenchymal chondrogenesis is accompanied by altered N‐cadherin‐related functions
Author(s) -
Tufan A. Cevik,
Tuan Rocky S.
Publication year - 2001
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.00-0784fje
Subject(s) - chondrogenesis , mesenchymal stem cell , cadherin , wnt signaling pathway , microbiology and biotechnology , limb development , chemistry , sox9 , anatomy , biology , signal transduction , gene , embryo , biochemistry , gene expression , cell
ABSTRACT It has been suggested that Wnt proteins play essential roles in the regulation of limb development and morphogenesis. We have analyzed the effects of RCAS retroviral‐mediated misexpression of Wnt‐5a and Wnt‐7a, two Wnt genes expressed during normal limb development, on chondrogenesis in high‐density micromass cultures of chick limb bud mesenchymal cells. Wnt‐ 7a misexpression inhibited chondrogenesis in vitro, whereas Wnt‐5a did not. Analysis of cellular condensation and precartilage aggregate formation revealed that the inhibitory effect of Wnt‐7a is unlikely to act at the cellular condensation step but, instead, influences the actual chondrogenic differentiation process. During early condensation, N‐cadherin expression within the cellular aggregates in Wnt‐7a cultures was slightly delayed, whereas Wnt‐5a cultures appeared similar to control cultures. With the initiation of differentiation, Wnt‐5a and control cultures showed down‐ regulation of N‐cadherin and up‐regulation of collagen type II expression, whereas Wnt‐7a cultures showed persistent, high levels of N‐cadherin expression both at the mRNA and protein levels, up to 72 h, and nearly no collagen type II expression. Wnt‐7a misexpression was also accompanied by an initial increase in the serine/threonine phosphorylation of β‐catenin and N‐ cadherin, events known to affect N‐cadherin turnover and stabilization of β‐catenin/N‐cadherin cell adhesion complex, during chondrogenic differentiation. Wnt regulation of limb mesenchymal chondrogenesis is thus likely to involve modulation of N‐cadherin expression and function. In addition, Wnt‐7a misexpression stimulates the proliferation of limb mesenchymal cells in vitro, possibly contributing to its chondro‐inhibitory effect. Finally, the differences between Wnt‐5a and Wnt‐7a effects suggest functional diversity within the Wnt family.