Function of LEF1 in early mammary development

LEF1, a member of the LEF1/TCF transcription factors, is a component of the canonical Wnt-signalling pathway. The Lef1 knockout mouse (Grosschedl) lacks hair, vibrissae, teeth, and mammary glands–all derivatives of the ectoderm. Experimental analysis of the role of LEF1 in tooth development has revealed an entirely non-cell-autonomous function–rather surprising for a component of a signal reception pathway. In fact, Lef1-deficient tooth development can be fully rescued by recombinant fibroblast growth factors, indicating that the sole function of LEF1 in this organ is to link Wnt- and fibroblast growth factor-signalling activities. Apparently, LEF1 is a crucial transcription factor regulating epithelial–mesenchymal interaction. Basically, a similar role of LEF1 was found in vibrissa (whisker) development but its function in mammary gland development remains enigmatic. Mammary buds do form in E11/12 mutant embryos, persisting (with variable penetrance) for 2–3 days, but no glands ever grow out. Although mutant mammary glands occasionally do develop in culture, no defined factors were found to be capable of rescuing mammary development. Our preliminary results indicate an additional function of LEF1 in mammary development, possibly in establishing mammary versus epidermal cell fate.