Temporal induction of the homeodomain transcription factor Nkx2-1 is sufficient to respecify foregut and hindgut endoderm to a pulmonary fate in Xenopus laevis.

The ability of transcription factors (TFs) to regulate cell fate decisions is paramount in developmental, homeostatic, and pathogenic contexts. The homeodomain TF NKX2-1 is an essential and evolutionarily conserved master regulator of pulmonary fate in vertebrates. In this study, we tested the spatial-temporal ability of Xenopus and Human NKX2-1 to respecify foregut and hindgut endoderm in developing Xenopus laevis embryos into a pulmonary fate, as indicated by expression of pulmonary surfactant genes sftpc and sftpb . Interestingly, we find that both Human and Xenopus NKX2-1 can induce the ectopic expression of pulmonary surfactant genes in foregut and hindgut endoderm over a wide range of developmental times, as well as suppress the expression of midgut and hindgut specific genes. These results suggest a single pulmonary TF can reprogram developing endoderm and specify pulmonary fate. In addition, our work provides a comparative platform for future studies investigating how mutations in Human NKX2-1 may affect its transcriptional activity.