Center for Stem Cell and Organoid Medicine (CuSTOM), Division of Developmental Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
University of Cincinnati, College of Medicine, Department of Pediatrics, Cincinnati, Ohio, USA.
Dev Growth Differ. 2022 Sep;64(7):347-361. doi: 10.1111/dgd.12807. Epub 2022 Sep 16.
Ventx2 is an Antennapedia superfamily/NK-like subclass homeodomain transcription factor best known for its roles in the regulation of early dorsoventral patterning during Xenopus gastrulation and in the maintenance of neural crest multipotency. In this work we characterize the spatiotemporal expression pattern of ventx2 in progenitor cells of the Xenopus respiratory system epithelium. We find that ventx2 is directly induced by BMP signaling in the ventral foregut prior to nkx2-1, the earliest epithelial marker of the respiratory lineage. Functional studies demonstrate that Ventx2 regulates the number of Nkx2-1/Sox9+ respiratory progenitor cells induced during foregut development, the timing and level of surfactant protein gene expression, and proper tracheal-esophageal separation. Our data suggest that Ventx2 regulates the balance of respiratory progenitor cell expansion and differentiation. While the ventx gene family has been lost from the mouse genome during evolution, humans have retained a ventx2-like gene (VENTX). Finally, we discuss how our findings might suggest a possible function of VENTX in human respiratory progenitor cells.
Ventx2 是 Antennapedia 超家族/NK 样亚类同源结构域转录因子，以其在非洲爪蟾原肠胚形成过程中对早期背腹模式形成的调节作用以及对神经嵴多能性的维持作用而闻名。在这项工作中，我们描述了 Ventx2 在非洲爪蟾呼吸系统上皮祖细胞中的时空表达模式。我们发现 Ventx2 在 nkx2-1（呼吸谱系的最早上皮标志物）之前，直接被 BMP 信号诱导在腹侧前肠中表达。功能研究表明，Ventx2 调节在前肠发育过程中诱导的 Nkx2-1/Sox9+呼吸祖细胞的数量、表面活性剂蛋白基因表达的时间和水平以及气管食管分离的适当性。我们的数据表明，Ventx2 调节呼吸祖细胞扩增和分化的平衡。虽然 Ventx 基因家族在进化过程中从老鼠基因组中丢失，但人类保留了一个 Ventx2 样基因（VENTX）。最后，我们讨论了我们的发现如何暗示 VENTX 在人类呼吸祖细胞中的可能功能。
