BackgroundIn the face of changing environmental conditions, the mechanisms underlying stress responses in diverse organisms are of increasing interest. In vertebrates, Drosophila, and Caenorhabditis elegans, FoxO transcription factors mediate cellular responses to stress, including oxidative stress and dietary restriction. Although FoxO genes have been identified in early-arising animal lineages including sponges and cnidarians, little is known about their roles in these organisms.Methods/Principal FindingsWe have examined the regulation of FoxO activity in members of the well-studied cnidarian genus Hydra. We find that Hydra FoxO is expressed at high levels in cells of the interstitial lineage, a cell lineage that includes multipotent stem cells that give rise to neurons, stinging cells, secretory cells and gametes. Using transgenic Hydra that express a FoxO-GFP fusion protein in cells of the interstitial lineage, we have determined that heat shock causes localization of the fusion protein to the nucleus. Our results also provide evidence that, as in bilaterian animals, Hydra FoxO activity is regulated by both Akt and JNK kinases.ConclusionsThese findings imply that basic mechanisms of FoxO regulation arose before the evolution of bilaterians and raise the possibility that FoxO is involved in stress responses of other cnidarian species, including corals.

SUMMARYThe atypical cadherin Fat is a conserved regulator of planar cell polarity, but the mechanisms by which Fat controls cell shape and tissue structure are not well understood. Here, we show that Fat is required for the planar polarized organization of actin denticle precursors, adherens junction proteins and microtubules in the epidermis of the late Drosophila embryo. In wild-type embryos, spatially regulated cell-shape changes and rearrangements organize cells into highly aligned columns. Junctional remodeling is suppressed at dorsal and ventral cell boundaries, where adherens junction proteins accumulate. By contrast, adherens junction proteins fail to accumulate to the wild-type extent and all cell boundaries are equally engaged in junctional remodeling in fat mutants. The effects of loss of Fat on cell shape and junctional localization, but not its role in denticle organization, are recapitulated by mutations in Expanded, an upstream regulator of the conserved Hippo pathway, and mutations in Hippo and Warts, two kinases in the Hippo kinase cascade. However, the cell shape and planar polarity defects in fat mutants are not suppressed by removing the transcriptional co-activator Yorkie, suggesting that these roles of Fat are independent of Yorkie-mediated transcription. The effects of Fat on cell shape, junctional remodeling and microtubule localization are recapitulated by expression of activated Notch. These results demonstrate that cell shape, junctional localization and cytoskeletal planar polarity in the Drosophila embryo are regulated by a common signal provided by the atypical cadherin Fat and suggest that Fat influences tissue organization through its role in polarized junctional remodeling. DEVELOPMENT 434 Donoughe and DiNardo, 2011). Despite substantial progress in understanding the upstream signals that regulate Fat activity, the cellular and molecular mechanisms by which Fat controls planar tissue organization are not well understood. Fat and Ds are asymmetrically localized within cells (Ambegaonkar et al., 2012;Bosveld et al., 2012;Brittle et al., 2012) and could influence cell polarity directly or through the regulation of downstream effectors. However, the relationship between these molecular asymmetries and the asymmetric shapes and behaviors of cells is not clear. Fat and Ds regulate the localization and activity of Frizzled pathway proteins (Adler et al., 1998;Strutt and Strutt, 2002;Yang et al., 2002;Ma et al., 2003), but some effects of Fat and Ds are independent of Frizzled (Casal et al., 2006;Donoughe and DiNardo, 2011). Fat/Ds signaling produces an asymmetric localization of the unconventional myosin Dachs, which is required for cell and tissue shape (Mao et al., 2006;Rogulja et al., 2008;Mao et al., 2011b;Bosveld et al., 2012). Fat binds to Atrophin (Grunge -FlyBase), a transcriptional regulator that is required for planar polarity in the eye (Zhang et al., 2002;Fanto et al., 2003;Saburi et al., 2012). Ds regulates microtubule organization in the wing and has been proposed to influ...

Recent evidence suggests that Fragile X syndrome and other types of autism are associated with immune system defects. Here, O’Connor et al. find that Drosophila Fmr1 mutants, a model for Fragile X syndrome, exhibit defects in phagocytosis by innate immune cells in both the body and the brain.