Ehlermann Julia, Pfisterer Petra, Schorle Hubert
Institute for Pathology, Department of Developmental Pathology, University of Bonn Medical School, Bonn, Germany.
Anat Rec A Discov Mol Cell Evol Biol. 2003 Aug;273(2):677-80. doi: 10.1002/ar.a.10089.
Krüppel-like factor 4 (Klf4) belongs to the family of transcription factors that are thought to be involved in the regulation of epithelial and germ cell differentiation, based on their expression in postproliferative cells of the skin, gut, and testes. Gene ablation experiments suggest that Klf4 plays a role in keratinocyte differentiation, since mice lacking Klf4 fail to establish proper barrier function and, as a consequence, die postnatally due to dehydration. Recent studies have shown that Klf4 is also expressed in postnatal male mice, in postmeiotic sperm cells undergoing terminal differentiation into sperm cells. However, prior to the current study, the expression pattern of Klf4 during early and mid-embryogenesis had not been examined. Here we demonstrate that Klf4 transcripts can be detected from embryonic day 4.5 (E4.5) on in the developing conceptus, and that Klf4 expression before E10 is restricted to extraembryonic tissues. The embryo proper displays a highly dynamic and changing Klf4 signal from E10 of murine development on. In addition to being expressed in a stripe of mesenchymal cells extending from the forelimb bud rostrally over the branchial arches to the developing eye, Klf4 is also expressed in the mesenchyme surrounding the nasal pit at day E11.5. In addition, Klf4 has been detected in the apical ectodermal ridge and adjacent mesenchymal cells in the limb buds, and in mesenchymal cells of the developing body wall in trunk areas. These findings suggest that Klf4 plays an important role in regulating cellular proliferation, which underlies the morphogenetic changes that shape the developing embryo.
Krüppel样因子4(Klf4)属于转录因子家族,基于其在皮肤、肠道和睾丸的增殖后细胞中的表达,被认为参与上皮细胞和生殖细胞分化的调控。基因敲除实验表明Klf4在角质形成细胞分化中起作用,因为缺乏Klf4的小鼠无法建立适当的屏障功能,因此在出生后因脱水而死亡。最近的研究表明,Klf4也在出生后的雄性小鼠中表达,即在经历终末分化成为精子细胞的减数分裂后精子细胞中表达。然而,在本研究之前,尚未检测到Klf4在胚胎早期和中期发育过程中的表达模式。在这里,我们证明从胚胎第4.5天(E4.5)开始在发育中的胚胎中就能检测到Klf4转录本,并且在E10之前Klf4的表达仅限于胚外组织。从小鼠发育的E10开始,胚胎本身显示出高度动态变化的Klf4信号。除了在从前肢芽向头侧延伸越过鳃弓到发育中的眼睛的间充质细胞条带中表达外,在E11.5天时Klf4也在鼻凹周围的间充质中表达。此外,在肢芽的顶端外胚层嵴和相邻间充质细胞以及躯干区域发育中的体壁间充质细胞中也检测到了Klf4。这些发现表明Klf4在调节细胞增殖中起重要作用,而细胞增殖是塑造发育中胚胎形态发生变化的基础。