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

在非洲爪蟾中,同源域转录因子Nkx2-1的瞬时诱导足以将前肠和后肠内胚层重新指定为肺部命运。

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Abstract

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.

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