Schindler Adam J, Sherwood David R
Department of Biology; Duke University ; Durham, NC USA.
Worm. 2014 Dec 31;3(4):e979658. doi: 10.4161/21624054.2014.979658. eCollection 2014 Oct-Dec.
After embryogenesis, developing organisms typically secure their own nutrients to enable further growth. The fitness of an organism depends on developing when food is abundant and slowing or stopping development during periods of scarcity. Although several key pathways that link nutrition with development have been identified, a mechanistic understanding of how these pathways coordinate growth with nutritional conditions is lacking. We took advantage of the stereotyped development and experimental accessibility of C. elegans to study nutritional control of late larval development. We discovered that C. elegans larval development is punctuated by precisely time checkpoints that globally arrest growth when nutritional conditions are unfavorable. Arrest at the checkpoints is regulated by insulin- and insulin-like signaling and steroid hormone signaling. These pathways are conserved in mammals, suggesting that similar mechanisms could regulate growth and development in humans. We highlight several implications of our research, including quiescence of diverse cellular behaviors as an adaptive response to unfavorable growth conditions, the existence of oscillatory checkpoints that coordinate development across tissues, and the connections between systemic and cell-autonomous regulators of nutritional response. Together, our findings describe a fascinating developmental strategy in C. elegans that we expect will not only provide insight into nutritional regulation of development, but also into poorly understood cellular processes such as quiescence and aging.
胚胎发育完成后，发育中的生物体通常会获取自身的营养物质以实现进一步生长。生物体的适应性取决于在食物丰富时进行发育，并在食物匮乏时期减缓或停止发育。尽管已经确定了几条将营养与发育联系起来的关键途径，但对于这些途径如何将生长与营养状况协调起来，仍缺乏机制上的理解。我们利用秀丽隐杆线虫刻板的发育过程和实验可及性，来研究幼虫后期发育的营养控制。我们发现，秀丽隐杆线虫的幼虫发育被精确的时间检查点所打断，当营养条件不利时，这些检查点会全面阻止生长。在这些检查点的停滞是由胰岛素和胰岛素样信号以及类固醇激素信号调节的。这些途径在哺乳动物中是保守的，这表明类似的机制可能在人类中调节生长和发育。我们强调了我们研究的几个意义，包括多种细胞行为的静止作为对不利生长条件的适应性反应、协调组织间发育的振荡检查点的存在，以及营养反应的全身调节因子和细胞自主调节因子之间的联系。总之，我们的发现描述了秀丽隐杆线虫中一种迷人的发育策略，我们预计这不仅将为发育的营养调节提供见解，还将为诸如静止和衰老等了解甚少的细胞过程提供见解。
