title: 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.
authors.affiliation: Department of Zoology, Michigan State University, East Lansing, Michigan, United States of America.
authors.forename: Hui Yuan
authors.initials: HY
authors.lastname: Tang
authors.forename: Martha S B
authors.initials: MS
authors.lastname: Smith-Caldas
authors.forename: Michael V
authors.initials: MV
authors.lastname: Driscoll
authors.forename: Samy
authors.initials: S
authors.lastname: Salhadar
authors.forename: Alexander W
authors.initials: AW
authors.lastname: Shingleton
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D059647:Gene-Environment Interaction; D005835:Genitalia / Q000254:growth & development / Q000378:metabolism; D007109:Immunity / Q000235:genetics; D007328:Insulin / Q000235:genetics* / Q000378:metabolism*; D008136:Longevity / Q000235:genetics; D054647:Nutrigenomics; D009747:Nutritional Physiological Phenomena / Q000235:genetics*; D009929:Organ Size / Q000235:genetics*; D009928:Organ Specificity / Q000235:genetics; D010641:Phenotype; D015398:Signal Transduction
chemical_list: D029721:Drosophila Proteins; C477334:FOXO protein, Drosophila; D051858:Forkhead Transcription Factors; D007328:Insulin
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