Liu Xiaolin, Huang Sizhou, Ma Jun, Li Chun, Zhang Yaoguang, Luo Lingfei
Key Laboratory of Aquatic Organism Reproduction and Development, Ministry of Education, Key Laboratory of Aquatic Science of Chongqing, School of Life Science, Southwest University, Beibei, Chongqing, China.
J Cell Biol. 2009 Mar 23;184(6):805-15. doi: 10.1083/jcb.200806074.
The cell cycle needs to strictly coordinate with developmental processes to ensure correct generation of the body plan and different tissues. However, the molecular mechanism underlying the coordination remains largely unknown. In this study, we investigate how the cell cycle coordinates gastrulation cell movements in zebrafish. We present a system to modulate the cell cycle in early zebrafish embryos by manipulating the geminin-Cdt1 balance. Alterations of the cell cycle change the apoptotic level during gastrulation, which correlates with the nuclear level of antiapoptotic nuclear factor kappaB (NF-kappaB). NF-kappaB associates with the Snail1a promoter region on the chromatin and directly activates Snail1a, an important factor controlling cell delamination, which is the initial step of mesendodermal cell movements during gastrulation. In effect, the cell cycle coordinates the delamination of mesendodermal cells through the transcription of Snail1a. Our results suggest a molecular mechanism by which NF-kappaB and Snail1a coordinate the cell cycle through gastrulation.
细胞周期需要与发育过程严格协调,以确保正确生成身体结构和不同组织。然而,这种协调背后的分子机制在很大程度上仍不清楚。在本研究中,我们探究了细胞周期如何协调斑马鱼原肠胚形成过程中的细胞运动。我们提出了一个通过操纵geminin-Cdt1平衡来调节斑马鱼早期胚胎细胞周期的系统。细胞周期的改变会改变原肠胚形成过程中的凋亡水平,这与抗凋亡核因子κB(NF-κB)的核水平相关。NF-κB与染色质上的Snail1a启动子区域结合,并直接激活Snail1a,Snail1a是控制细胞分层的重要因子,而细胞分层是原肠胚形成过程中中内胚层细胞运动的起始步骤。实际上,细胞周期通过Snail1a的转录来协调中内胚层细胞的分层。我们的结果表明了一种分子机制,即NF-κB和Snail1a通过原肠胚形成过程来协调细胞周期。