FOXO Regulates Organ-Specific Phenotypic Plasticity In Drosophila

Abstract

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.

Positional specification in the segmental growth pattern of an early arthropod

“…However, if segment differential growth rate in A. koninckii was under the control of a morphogen signal, with effect, for instance, on the level of expression of some growth hormone receptors or of members of the signalling pathways downstream of them [5,28,29], as is likely when it is considered that genes and hormones involved in tissue growth are remarkably conserved in all animals [30], this signal was apparently transduced linearly into an isomorphic growth gradient response.…”

Complex cis-regulatory landscape of the insulin receptor gene underlies the broad expression of a central signaling regulator

“…Our study provides new insights into the transcriptional regulation mediated by FOXO, a key player in nutritionally driven developmental plasticity and insulin sensitivity (Tang et al, 2011). Feedback regulation by FOXO transcription factors controls the expression of InR (Jünger et al, 2003;Puig et al, 2003;Puig and Tjian, 2005).…”

Caste development and evolution in ants: it's all about size

“…Ovariole number varies with body size across a wide range of taxa, and in D. melanogaster this is mediated by the insulin/insulin-like signaling pathway (IIS) (Honeǩ, 1993;Honegger et al, 2008;Tu and Tatar, 2003;Green and Extavour, 2014). IIS may also be responsible for the reduction in eye size and wing size observed in small D. melanogaster individuals (Tang et al, 2011). More extreme variation in tissue growth has been observed in other insects, where it is associated with IIS, but also JH, ecdysone and even the hedgehog signaling pathway (Lobbia et al, 2003;Emlen et al, 2012;Gotoh et al, 2014;Niitsu et al, 2014;Kijimoto and Moczek, 2016;Xu et al, 2015; see also the excellent discussion in Zinna et al, 2016).…”