Department of Genetics and Evolution, Institute of Genetics and Genomics (iGE3), Faculty of Sciences, University of Geneva, 30 Quai Ernest Ansermet, Geneva 4 1211, Switzerland.
Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, Basel 4058, Switzerland.
Sci Adv. 2022 Dec 23;8(51):eabo0694. doi: 10.1126/sciadv.abo0694.
The molecular mechanisms that maintain cellular identities and prevent dedifferentiation or transdifferentiation remain mysterious. However, both processes are transiently used during animal regeneration. Therefore, organisms that regenerate their organs, appendages, or even their whole body offer a fruitful paradigm to investigate the regulation of cell fate stability. Here, we used as a model system and show that Zic4, whose expression is controlled by Wnt3/β-catenin signaling and the Sp5 transcription factor, plays a key role in tentacle formation and tentacle maintenance. Reducing expression suffices to induce transdifferentiation of tentacle epithelial cells into foot epithelial cells. This switch requires the reentry of tentacle battery cells into the cell cycle without cell division and is accompanied by degeneration of nematocytes embedded in these cells. These results indicate that maintenance of cell fate by a Wnt-controlled mechanism is a key process both during homeostasis and during regeneration.
维持细胞身份、防止去分化或转分化的分子机制仍然神秘。然而,这两个过程在动物再生过程中都是短暂发生的。因此,能够再生其器官、附肢甚至整个身体的生物体为研究细胞命运稳定性的调控提供了一个富有成效的范例。在这里,我们使用 作为模型系统,并表明其表达受 Wnt3/β-catenin 信号和 Sp5 转录因子调控的 Zic4 在触手形成和维持中发挥关键作用。降低 表达足以诱导触手表皮细胞向足表皮细胞的转分化。这种转变需要触手电池细胞重新进入细胞周期而不进行细胞分裂,并且伴随着嵌入这些细胞中的纤毛细胞的退化。这些结果表明,Wnt 控制的机制维持细胞命运是体内平衡和再生过程中的关键过程。