LEF1 EXPRESSION IS ACTIVATED BY BMP-4 AND REGULATES INDUCTIVE TISSUE INTERACTIONS IN TOOTH AND HAIR DEVELOPMENT

Targeted inactivation of the murine gene encoding the transcription fa ctor LEF-1 abrogates the formation of organs that depend on epithelial -mesenchymal tissue interactions. In this study we have recombined epi thelial and mesenchymal tissues from normal and LEF-1-deficient embryo s at different stages of development to define the LEF-1-dependent ste ps in tooth and whisker organogenesis. At the initiation of organ deve lopment, formation of the epithelial primordium of the whisker but not tooth is dependent on mesenchymal Lef1 gene expression. Subsequent fo rmation of a whisker and tooth mesenchymal papilla and completion of o rganogenesis require transient expression of Lef1 in the epithelium. T hese experiments indicate that the effect of Lef1 expression is transm itted from one tissue to the other. In addition, the finding that the expression of Lef1 can be activated by bone morphogenetic protein 4 (B MP-4) suggests a regulatory role of this transcription factor in BMP-m ediated inductive tissue interactions.