The Nuclear Receptor Seven Up Regulates Genes Involved in Immunity and Xenobiotic Response in the AdultDrosophilaFemale Fat Body

Abstract

The physiology of organisms depends on inter-organ communication in response to changes in the environment. Nuclear receptors are broadly expressed transcription factors that respond to circulating molecules to control many biological processes, including immunity, detoxification, and reproduction. Although the tissue-intrinsic roles of nuclear receptors in reproduction have been extensively studied, there is increasing evidence that nuclear receptor signaling in peripheral tissues can also influence oogenesis. We previously showed that the Drosophila nuclear receptor Seven up (Svp) is required in the adult fat body to regulate distinct steps of oogenesis; however, the relevant downstream targets of Svp remain unknown. Here, we took an RNA sequencing approach to identify candidate Svp targets specifically in the adult female fat body that might mediate this response. svp knockdown in the adult female fat body significantly downregulated immune genes involved in the first line of pathogen defense, suggesting a role for Svp in stimulating early immunity. In addition, we found that Svp transcriptionally regulates genes involved in each step of the xenobiotic detoxification response. Based on these findings, we propose a testable model in which Svp functions in the adult female fat body to stimulate early defense against pathogens and facilitate detoxification as part of its mechanisms to promote oogenesis.

Xenobiotic responses in insects

“…Besides HR96, Seven up (Svp), another nuclear hormone receptor in D. melanogaster, was newly reported also related to the expression of several detoxification genes. When svp was knocked down in the adult fat body, the expression of Cyp12d-1, Cyp4e3, Cyp4p2, and GstD5 was clearly reduced (Weaver & Drummond-Barbosa, 2020). However, whether Svp plays a role in induced expression of these targets after toxin contaction, is still an open question about the role of Svp in xenobiotic response exist.…”

The Dynamic Regulation of mRNA Translation and Ribosome Biogenesis During Germ Cell Development and Reproductive Aging

“…Work in Drosophila has illustrated how signals from fat tissue can modulate mTOR signaling within germline stem cells ( Armstrong et al, 2014 ). Subsequent studies from the Drummond-Barbosa lab have continued to characterize how interorgan communication influences germ cell development in flies ( Matsuoka et al, 2017 ; Armstrong and Drummond-Barbosa, 2018 ; Weaver and Drummond-Barbosa, 2018 , 2019 , 2020 , 2021 ). Work from the Conti and Eppig labs, among others, shows that bidirectional communication between developing oocytes and their somatic cell neighbors also plays an important role in mammalian germ cell development ( Chen et al, 2013 ; Wigglesworth et al, 2013 ).…”

Origin and Development of the Adipose Tissue, a Key Organ in Physiology and Disease

“…Recently, Weaver and Drummond-Barbosa showed that the nuclear receptor Svp regulates a number of factors involved in immunity and xenobiotic detoxification responses in adult female FB ( Weaver and Drummond-Barbosa, 2020 ). Specifically, Svp would acts as the first line of defence against infections, regulating genes involved in the capture and elimination of foreign pathogens.…”

“…Svp also regulates the expression of genes encoding members of the CYP450 family involved in the initiation of phase I of the xenobiotic detoxification response. Reduction of svp expression results in the upregulation of genes encoding Metallothionein A and B ( MtnA and MtnB ) ( Weaver and Drummond-Barbosa, 2020 ). MtnA and B are enzymes involved in heavy metal detoxification and protection against free radicals and have been involved in the response to xenobiotic and immune stress ( Bonneton et al, 1996 ).…”

“…MtnA and B are enzymes involved in heavy metal detoxification and protection against free radicals and have been involved in the response to xenobiotic and immune stress ( Bonneton et al, 1996 ). It has been suggested that a reduced activity of Svp could lead to a toxic scenario, which would need MtnA and B activity to eliminate this toxicity ( Weaver and Drummond-Barbosa, 2020 ) ( Figure 4 ).…”