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Significance Paralogs represent genetic redundancy and survive purifying selection by evolving overlapping and distinct functions. In multicellular organisms, such functional diversification can manifest as tissue and cell-type-specific expression, which masks possible selective pressure for genetic redundancy within a single cell type. Using in vivo genetic and genomic analyses, we show that although the four mammalian Lef/Tcf transcription factors have evolved organ-specific functions, they function additively and redundantly, depending on gene dosage, to promote lung epithelial progenitors and do so in a monotonic, positive manner with beta-catenin in the canonical Wnt signaling pathway.

Redundant and additive functions of the four Lef/Tcf transcription factors in lung epithelial progenitors