FGF4, a direct target of LEF1 and Wnt signaling, can rescue the arrest of tooth organogenesis in Lef1-/- mice

被引:199
作者
Kratochwil, K
Galceran, J
Tontsch, S
Roth, W
Grosschedl, R
机构
[1] Univ Munich, Gene Ctr, D-81377 Munich, Germany
[2] Univ Munich, Inst Biochem, D-81377 Munich, Germany
[3] Austrian Acad Sci, Inst Mol Biol, A-5020 Salzburg, Austria
关键词
LEF1; Wnt; FGF; epithelial-mesenchymal interactions;
D O I
10.1101/gad.1035602
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Lymphoid enhancer factor (LEF1), a nuclear mediator of Writ signaling, is required for the formation of organs that depend on inductive interactions between epithelial and mesenchymal tissues. In previous tissue recombination experiments with normal and Lef1(-/-) tooth germs, we found that the effect of LEF1 expression in the epithelium is tissue nonautonomous and transferred to the subjacent mesenchyme. Here we examine the molecular basis for LEF1 function and find that the epithelium of the developmentally arrested Lef1(-/-) tooth rudiments fails to express Fgf4, Shh, and Bmp4, but not Wnt10a. We identify the Fgf4 gene as a direct transcriptional target for LEF1 and show that beads soaked with recombinant FGF4 protein can fully overcome the developmental arrest of Lef1(-/-) tooth germs. In addition, we find that FGF4 beads induce rapidly the expression of Fgf3 in dental mesenchyme and that both epithelial and mesenchymal FGF proteins induce the delayed expression of Shh in the epithelium. Taken together, these data indicate that a single target of LEF1 can account for the function of LEF1 in tooth development and for a relay of a Wnt signal reception to a cascade of FGF signaling activities, allowing for a sequential and reciprocal communication between epithelium and mesenchyme.
引用
收藏
页码:3173 / 3185
页数:13
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