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

**Authors:** Brian A Hyatt, Erin Lundberg, Rachael Eye, Scott A Rankin, Aaron M Zorn

PMC · DOI: 10.17912/micropub.biology.001610 · microPublication Biology · 2025-05-07

## TL;DR

The study shows that the NKX2-1 transcription factor can reprogram gut cells in frog embryos to take on lung cell characteristics.

## Contribution

The study demonstrates that temporal induction of NKX2-1 is sufficient to respecify endoderm to a pulmonary fate in Xenopus.

## Key findings

- Human and Xenopus NKX2-1 induce pulmonary surfactant genes in foregut and hindgut endoderm.
- NKX2-1 suppresses midgut and hindgut-specific gene expression.
- A single pulmonary transcription factor can reprogram endoderm fate.

## 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.

## Linked entities

- **Genes:** NKX2-1 (NK2 homeobox 1) [NCBI Gene 7080], SFTPC (surfactant protein C) [NCBI Gene 6440], SFTPB (surfactant protein B) [NCBI Gene 6439]
- **Proteins:** NKX2-1 (NK2 homeobox 1)
- **Species:** Xenopus laevis (taxon 8355)

## Full-text entities

- **Genes:** nkx2-1.L (NK2 homeobox 1 L homeolog) [NCBI Gene 373626] {aka Xnkx-2.1, nkx2-1, nkx2.1, titf1, titf1-A, ttf1}, sftpc.S (surfactant, pulmonary-associated protein C S homeolog) [NCBI Gene 779071] {aka SP-C, SPC, sftpc, surfc, xSP-C}, sftpb.L (surfactant, pulmonary-associated protein B L homeolog) [NCBI Gene 779297] {aka SP-B, sftpb, xSP-B}
- **Species:** Homo sapiens (human, species) [taxon 9606], Xenopus laevis (African clawed frog, species) [taxon 8355]

## Full text

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## Figures

1 figure with captions in the complete paper: https://tomesphere.com/paper/PMC12096181/full.md

## References

38 references — full list in the complete paper: https://tomesphere.com/paper/PMC12096181/full.md

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Source: https://tomesphere.com/paper/PMC12096181