Department of Biology, University of Copenhagen, 2100, Denmark.
Department of Biology, University of Copenhagen, 2100, Denmark
Genetics. 2020 Oct;216(2):269-313. doi: 10.1534/genetics.120.303095.
The control of body and organ growth is essential for the development of adults with proper size and proportions, which is important for survival and reproduction. In animals, adult body size is determined by the rate and duration of juvenile growth, which are influenced by the environment. In nutrient-scarce environments in which more time is needed for growth, the juvenile growth period can be extended by delaying maturation, whereas juvenile development is rapidly completed in nutrient-rich conditions. This flexibility requires the integration of environmental cues with developmental signals that govern internal checkpoints to ensure that maturation does not begin until sufficient tissue growth has occurred to reach a proper adult size. The Target of Rapamycin (TOR) pathway is the primary cell-autonomous nutrient sensor, while circulating hormones such as steroids and insulin-like growth factors are the main systemic regulators of growth and maturation in animals. We discuss recent findings in showing that cell-autonomous environment and growth-sensing mechanisms, involving TOR and other growth-regulatory pathways, that converge on insulin and steroid relay centers are responsible for adjusting systemic growth, and development, in response to external and internal conditions. In addition to this, proper organ growth is also monitored and coordinated with whole-body growth and the timing of maturation through modulation of steroid signaling. This coordination involves interorgan communication mediated by a insulin-like peptide 8 in response to tissue growth status. Together, these multiple nutritional and developmental cues feed into neuroendocrine hubs controlling insulin and steroid signaling, serving as checkpoints at which developmental progression toward maturation can be delayed. This review focuses on these mechanisms by which external and internal conditions can modulate developmental growth and ensure proper adult body size, and highlights the conserved architecture of this system, which has made a prime model for understanding the coordination of growth and maturation in animals.
机体和器官生长的控制对于具有适当大小和比例的成年人的发育至关重要，这对于生存和繁殖至关重要。在动物中，成年体型由幼年生长的速度和持续时间决定，而这又受到环境的影响。在营养匮乏的环境中，生长需要更多的时间，因此可以通过延迟成熟来延长幼年生长阶段，而在营养丰富的条件下，幼年发育则迅速完成。这种灵活性需要将环境线索与发育信号相结合，这些信号控制内部检查点，以确保在组织生长达到适当的成年大小之前，不会开始成熟。雷帕霉素靶蛋白 (TOR) 途径是主要的细胞自主营养传感器，而循环激素如类固醇和胰岛素样生长因子是动物生长和成熟的主要系统调节剂。我们讨论了最近的研究结果表明，细胞自主环境和生长感应机制，涉及 TOR 和其他生长调节途径，这些途径都集中在胰岛素和类固醇中继中心，负责根据外部和内部条件调整全身生长和发育。此外，适当的器官生长还通过调节类固醇信号与全身生长和成熟的时间相协调。这种协调涉及到组织生长状态下的胰岛素样肽 8 介导的器官间通讯。总之，这些多种营养和发育线索反馈到控制胰岛素和类固醇信号的神经内分泌中枢，作为发育向成熟进展可以延迟的检查点。本综述重点介绍了外部和内部条件可以调节发育生长并确保适当成年体型的这些机制，并强调了该系统的保守结构，这使其成为理解动物生长和成熟协调的主要模型。
