In multicellular organisms, cell proliferation must be tightly coordinated with other developmental processes to form functional tissues and organs. Despite significant advances in our understanding of how the cell cycle is controlled by conserved cell‐cycle regulators (CCRs), how the cell cycle is coordinated with cell differentiation in metazoan organisms and how CCRs contribute to this process remain poorly understood. Here, we review the emerging roles of metazoan CCRs as intracellular proliferation‐differentiation coordinators in multicellular organisms. We illustrate how major CCRs regulate cellular events that are required for cell fate acquisition and subsequent differentiation. To this end, CCRs employ diverse mechanisms, some of which are separable from those underpinning the conventional cell‐cycle‐regulatory functions of CCRs. By controlling cell‐type‐specific specification/differentiation processes alongside the progression of the cell cycle, CCRs enable spatiotemporal coupling between differentiation and cell proliferation in various developmental contexts in vivo. We discuss the significance and implications of this underappreciated role of metazoan CCRs for development, disease and evolution.

中文翻译：

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后生动物 CCR 作为细胞周期和分化协调者的新兴作用

在多细胞生物中，细胞增殖必须与其他发育过程紧密协调以形成功能性组织和器官。尽管我们对细胞周期如何受保守细胞周期调节因子 (CCR) 控制的理解取得了重大进展，但细胞周期如何与后生生物的细胞分化协调以及 CCR 如何促进这一过程仍然知之甚少。在这里，我们回顾了后生动物 CCR 作为多细胞生物中细胞内增殖分化协调器的新兴作用。我们说明了主要的 CCR 如何调节细胞命运获得和随后的分化所需的细胞事件。为此，CCR 采用了多种机制，其中一些机制与支持 CCR 传统细胞周期调节功能的机制不同。通过控制细胞类型特异性规范/分化过程以及细胞周期的进展，CCR 能够在体内各种发育环境中实现分化和细胞增殖之间的时空耦合。我们讨论了后生动物 CCR 对发育、疾病和进化的这种未被充分认识的作用的重要性和影响。