Compensatory Roles of Foxa1 and Foxa2 during Lung Morphogenesis

Foxa1 and Foxa2 are closely related family members of the Foxa group of transcription factors that are coexpressed in subsets of respiratory epithelial cells throughout lung morphogenesis. Shared patterns of expression, conservation of DNA binding, and transcriptional activation domains indicate that they may serve complementary functions in the regulation of gene expression during lung morphogenesis. Whereas branching morphogenesis of the fetal lung occurs normally in the Foxa2Δ/Δ and Foxa1–/– mice, deletion of both Foxa1 and Foxa2 (in Foxa2Δ/Δ, Foxa1–/– mice) inhibited cell proliferation, epithelial cell differentiation, and branching. Dilation of terminal lung tubules and decreased branching were observed as early as embryonic day 12.5. Foxa1 and Foxa2 regulated and in the respiratory epithelial cells that the expression of in the that are branching morphogenesis. cell differentiation, as of expression of the cell and Foxa family members and transcriptional morphogenesis and cell during of the Foxa1 and Foxa2 are closely related family members of the Foxa group of transcription factors that are coexpressed in subsets of respiratory epithelial cells throughout lung morphogenesis. Shared patterns of expression, conservation of DNA binding, and transcriptional activation domains indicate that they may serve complementary functions in the regulation of gene expression during lung morphogenesis. Whereas branching morphogenesis of the fetal lung occurs normally in the Foxa2Δ/Δ and Foxa1–/– mice, deletion of both Foxa1 and Foxa2 (in Foxa2Δ/Δ, Foxa1–/– mice) inhibited cell proliferation, epithelial cell differentiation, and branching. Dilation of terminal lung tubules and decreased branching were observed as early as embryonic day 12.5. 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