McKeown C R, Thompson C K, Cline H T
Department of Molecular and Cellular Neuroscience, The Scripps Research Institute, La Jolla, CA 92037, USA
Department of Molecular and Cellular Neuroscience, The Scripps Research Institute, La Jolla, CA 92037, USA.
J Exp Biol. 2017 Feb 1;220(Pt 3):358-368. doi: 10.1242/jeb.151043. Epub 2016 Nov 10.
Many organisms confront intermittent nutrient restriction (NR), but the mechanisms to cope with nutrient fluctuations during development are not well understood. This is particularly true of the brain, the development and function of which is energy intensive. Here we examine the effects of nutrient availability on visual system development in Xenopus laevis tadpoles. During the first week of development, tadpoles draw nutrients from maternally provided yolk. Upon yolk depletion, animals forage for food. By altering access to external nutrients after yolk depletion, we identified a period of reversible stasis during tadpole development. We demonstrate that NR results in developmental stasis characterized by a decrease in overall growth of the animals, a failure to progress through developmental stages, and a decrease in volume of the optic tectum. During NR, neural progenitors virtually cease proliferation, but tadpoles swim and behave normally. Introducing food after temporary NR increased neural progenitor cell proliferation more than 10-fold relative to NR tadpoles, and cell proliferation was comparable to that of fed counterparts 1 week after delayed feeding. Delayed feeding also rescued NR-induced body length and tectal volume deficits and partially rescued developmental progression defects. Tadpoles recover from developmental stasis if food is provided within the first 9 days of NR, after which access to food fails to increase cell proliferation. These results show that early stages of tadpole brain development are acutely sensitive to fluctuations in nutrient availability and that NR induces developmental stasis from which animals can recover if food becomes available within a critical window.
许多生物都会面临间歇性的营养限制（NR），但在发育过程中应对营养波动的机制尚未得到充分理解。对于大脑而言尤其如此，因为大脑的发育和功能需要大量能量。在这里，我们研究了营养可利用性对非洲爪蟾蝌蚪视觉系统发育的影响。在发育的第一周，蝌蚪从母体提供的卵黄中获取营养。卵黄耗尽后，蝌蚪开始觅食。通过在卵黄耗尽后改变获取外部营养的机会，我们确定了蝌蚪发育过程中的一个可逆停滞期。我们证明，营养限制会导致发育停滞，其特征是动物整体生长减少、发育阶段进展失败以及视顶盖体积减小。在营养限制期间，神经祖细胞几乎停止增殖，但蝌蚪的游泳和行为正常。在短暂的营养限制后引入食物，相对于处于营养限制状态的蝌蚪，神经祖细胞增殖增加了10倍以上，并且在延迟喂食1周后，细胞增殖与正常喂食的蝌蚪相当。延迟喂食还挽救了营养限制引起的体长和顶盖体积缺陷，并部分挽救了发育进程缺陷。如果在营养限制的前9天内提供食物，蝌蚪可以从发育停滞中恢复，在此之后获取食物则无法增加细胞增殖。这些结果表明，蝌蚪大脑发育的早期阶段对营养可利用性的波动极为敏感，并且营养限制会诱导发育停滞，如果在关键窗口期内获得食物，动物可以从中恢复。
