Department of Zoology, Michigan State University, East Lansing, Michigan, United States of America.
PLoS Genet. 2011 Nov;7(11):e1002373. doi: 10.1371/journal.pgen.1002373. Epub 2011 Nov 10.
Phenotypic plasticity, the ability for a single genotype to generate different phenotypes in response to environmental conditions, is biologically ubiquitous, and yet almost nothing is known of the developmental mechanisms that regulate the extent of a plastic response. In particular, it is unclear why some traits or individuals are highly sensitive to an environmental variable while other traits or individuals are less so. Here we elucidate the developmental mechanisms that regulate the expression of a particularly important form of phenotypic plasticity: the effect of developmental nutrition on organ size. In all animals, developmental nutrition is signaled to growing organs via the insulin-signaling pathway. Drosophila organs differ in their size response to developmental nutrition and this reflects differences in organ-specific insulin-sensitivity. We show that this variation in insulin-sensitivity is regulated at the level of the forkhead transcription factor FOXO, a negative growth regulator that is activated when nutrition and insulin signaling are low. Individual organs appear to attenuate growth suppression in response to low nutrition through an organ-specific reduction in FOXO expression, thereby reducing their nutritional plasticity. We show that FOXO expression is necessary to maintain organ-specific differences in nutritional-plasticity and insulin-sensitivity, while organ-autonomous changes in FOXO expression are sufficient to autonomously alter an organ's nutritional-plasticity and insulin-sensitivity. These data identify a gene (FOXO) that modulates a plastic response through variation in its expression. FOXO is recognized as a key player in the response of size, immunity, and longevity to changes in developmental nutrition, stress, and oxygen levels. FOXO may therefore act as a more general regulator of plasticity. These data indicate that the extent of phenotypic plasticity may be modified by changes in the expression of genes involved in signaling environmental information to developmental processes.
表型可塑性是指单一基因型在应对环境条件时产生不同表型的能力，它在生物学中普遍存在，但对于调节可塑性反应程度的发育机制却几乎一无所知。特别是，为什么有些特征或个体对环境变量高度敏感，而有些特征或个体则不那么敏感，这一点还不清楚。在这里，我们阐明了调节表型可塑性一种特别重要形式表达的发育机制：发育营养对器官大小的影响。在所有动物中，发育营养都是通过胰岛素信号通路向生长器官发出信号的。果蝇器官在对发育营养的大小反应上存在差异，这反映了器官特异性胰岛素敏感性的差异。我们表明，这种胰岛素敏感性的变化是在叉头转录因子 FOXO 水平上调节的，FOXO 是一种负生长调节剂，当营养和胰岛素信号较低时，它会被激活。个体器官似乎通过器官特异性降低 FOXO 表达来减弱对低营养的生长抑制作用，从而降低其营养可塑性。我们表明，FOXO 表达对于维持器官特异性营养可塑性和胰岛素敏感性差异是必要的，而 FOXO 表达的器官自主性变化足以自主改变器官的营养可塑性和胰岛素敏感性。这些数据确定了一个基因（FOXO），它通过其表达的变化来调节可塑性反应。FOXO 被认为是大小、免疫和寿命对发育营养、应激和氧气水平变化的反应中的关键参与者。FOXO 因此可能作为可塑性的更一般调节剂。这些数据表明，参与将环境信息信号传递给发育过程的基因表达的变化可能会改变表型可塑性的程度。
