Model Animal Research Center of Nanjing University and MOE Key Laboratory of Model Animals for Disease Study, 12 Xuefu Road, Pukou High-Tech Zone, 210061 Nanjing, China.
Development. 2012 Nov;139(21):3950-61. doi: 10.1242/dev.082024. Epub 2012 Sep 19.
Klf4 is a transcription factor of the family of Kruppel-like factors and plays important roles in stem cell biology; however, its function during embryogenesis is unknown. Here, we report the characterization of a Klf4 homologue in Xenopus laevis during embryogenesis. Klf4 is transcribed both maternally and zygotically and the transcript is ubiquitous in embryos during germ-layer formation. Klf4 promotes endoderm differentiation in both Nodal/Activin-dependent and -independent manners. Moreover, Klf4 regulates anteroposterior body axis patterning via activation of a subset of genes in the Spemann organizer, such as Noggin, Dkk1 and Cerberus, which encode Nodal, Wnt and BMP antagonists. Loss of Klf4 function leads to the failure of germ-layer differentiation, the loss of responsiveness of early embryonic cells to inducing signals, e.g. Nodal/Activin, and the loss of transcription of genes involved in axis patterning. We conclude that Klf4 is required for germ-layer differentiation and body axis patterning by means of rendering early embryonic cells competent to differentiation signals.
Klf4 是 Kruppel 样因子家族的转录因子,在干细胞生物学中发挥重要作用;然而,其在胚胎发生中的功能尚不清楚。在这里,我们报道了非洲爪蟾胚胎发生中 Klf4 同源物的特征。Klf4 既以母源方式转录,也以合子方式转录,在胚胎发生过程中在胚胎中广泛存在。Klf4 以 Nodal/Activin 依赖和非依赖的方式促进内胚层分化。此外,Klf4 通过激活 Spemann 组织者中的一组基因,如编码 Nodal、Wnt 和 BMP 拮抗剂的 Noggin、Dkk1 和 Cerberus,来调节前后体轴模式形成。Klf4 功能丧失导致胚层分化失败,早期胚胎细胞对诱导信号(如 Nodal/Activin)的反应性丧失,以及参与轴模式形成的基因的转录丧失。我们的结论是,Klf4 通过使早期胚胎细胞有能力对分化信号作出反应,从而参与胚层分化和体轴模式形成。