Peunova Natalia, Scheinker Vladimir, Ravi Kandasamy, Enikolopov Grigori
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
Cell Cycle. 2007 Dec 15;6(24):3132-44. doi: 10.4161/cc.6.24.5146. Epub 2007 Oct 8.
The establishment of a vertebrate body plan during embryogenesis is achieved through precise coordination of cell proliferation and morphogenetic cell movements. Here we show that nitric oxide (NO) suppresses cell division and facilitates cell movements during early development of Xenopus, such that inhibition of NO synthase (NOS) increases proliferation in the neuroectoderm and suppresses convergent extension in the axial mesoderm and neuroectoderm. NO controls cell division and cell movement through two separate signaling pathways. Both rely on RhoA-ROCK signaling but can be distinguished by the involvement of either guanylate cyclase or the planar cell polarity regulator Dishevelled. Through the cGMP-dependent pathway, NO suppresses cell division by negatively regulating RhoA and controlling the nuclear distribution of ROCK and p21WAF1. Through the cGMP-independent pathway, NO facilitates cell movement by regulating the intracellular distribution and level of Dishevelled and the activity of RhoA, thereby controlling the activity of ROCK and regulating actin cytoskeleton remodeling and cell polarization. Concurrent control by NO helps ensure that the crucial processes of cell proliferation and morphogenetic movements are coordinated during early development.
胚胎发育过程中脊椎动物身体模式的建立是通过细胞增殖和形态发生细胞运动的精确协调来实现的。在此我们表明，一氧化氮（NO）在非洲爪蟾早期发育过程中抑制细胞分裂并促进细胞运动，使得一氧化氮合酶（NOS）的抑制增加了神经外胚层的增殖，并抑制了轴中胚层和神经外胚层的汇聚延伸。NO通过两条独立的信号通路控制细胞分裂和细胞运动。两者都依赖于RhoA-ROCK信号传导，但可通过鸟苷酸环化酶或平面细胞极性调节因子Dishevelled的参与来区分。通过cGMP依赖性途径，NO通过负调节RhoA并控制ROCK和p21WAF1的核分布来抑制细胞分裂。通过cGMP非依赖性途径，NO通过调节Dishevelled的细胞内分布和水平以及RhoA的活性来促进细胞运动，从而控制ROCK的活性并调节肌动蛋白细胞骨架重塑和细胞极化。NO的协同控制有助于确保在早期发育过程中细胞增殖和形态发生运动的关键过程得到协调。
