Ecdysone-dependent feedback regulation of prothoracicotropic hormone controls the timing of developmental maturation

Christensen, Christian; Kaburagi, Takashi; Nagy, Stanislav; Danielsen, E. Thomas; Texada, Michael J.; Halberg, Kenneth A.; Rewitz, Kim

doi:10.1242/dev.188110

Cited by 20 publications

(13 citation statements)

References 55 publications

(83 reference statements)

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“…Ecdysone was also shown to affect sleep (Ishimoto and Kitamoto, 2011), raising questions of the mechanism by which it does so and the cells on which it acts in adults. Our finding that ecdysone regulates sleep through metabolic mechanisms in glia is consistent with other metabolic functions attributed to it; for instance, it controls developmental transitions in response to nutrient signals (Christensen et al, 2020; Lee et al, 2000; Uyehara and Mckay, 2019; Xu et al, 2020; Yamanaka et al, 2013b). Indeed, ecdysone may affect the whole-body lipid profile to modulate physiology and behavior (Sieber and Spradling, 2015).…”

Section: Discussionsupporting

confidence: 89%

Ecdysone acts through cortex glia to regulate sleep in Drosophila

Haynes

Zhang

et al. 2022

Preprint

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Steroid hormones are attractive candidates for transmitting long-range signals to affect behavior. These lipid-soluble molecules derived from dietary cholesterol easily penetrate the brain and act through nuclear hormone receptors (NHRs) that function as transcription factors. To determine the extent to which NHRs affect sleep: wake cycles, we knocked down each of the 18 highly conserved NHRs found in Drosophila adults and report that the ecdysone receptor (EcR) and its direct downstream NHR Eip75B (E75) act in glia to regulate the rhythm and amount of sleep. Halloween genes, a set of ecdysone synthesis genes, have little to no expression in the fly brain, while mRNA levels of the ecdysone target E75 cycle in the fly head, suggesting that glial ecdysone comes from the periphery and may enter the brain more at night. Anti-EcR staining localizes to the cortex glia in the brain and functional screening of glial subtypes revealed that EcR functions in adult cortex glia to affect sleep. Cortex glia are implicated in lipid metabolism, which appears to be relevant for actions of ecdysone as ecdysone treatment reduces lipid droplet size in these cells. In addition, sleep-promoting effects of exogenous ecdysone are diminished in Lsd-2 mutant flies, which are lean and deficient in lipid accumulation. We propose that ecdysone is a systemic secreted factor that modulates sleep by stimulating lipid metabolism in cortex glia.

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Section: Discussionsupporting

confidence: 89%

Ecdysone acts through cortex glia to regulate sleep in Drosophila

Haynes

Zhang

et al. 2022

Preprint

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“…Recent study showed that ecdysone dose‐dependently affects PTTH transcription, promoting its expression at lower concentrations and inhibiting it at higher concentrations (Christensen et al ., 2020 ). The ecdysteriod titers in △Torso animals were dramatically reduced (Fig.…”

Section: Resultsmentioning

confidence: 99%

The receptor tyrosine kinase torso regulates ecdysone homeostasis to control developmental timing in Bombyx mori

Zhang

Liu

et al. 2020

Insect Science

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Insect growth and development are precisely controlled by hormone homeostasis. The prothoracicotropic hormone (PTTH) receptor, Torso, is a member of the receptor tyrosine kinase family in insects. Activation of Torso by PTTH triggers biosynthesis and release of the steroid hormone in the prothoracic gland (PG). Although numbers of genes functioning in steroid hormone synthesis and metabolism have been identified in insects, the PTTH transduction pathway via its receptor Torso is poorly understood. In the current study, we describe a loss-of-function analysis of Torso in the silkworm, Bombyx mori, by targeted gene disruption using the transgenic CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/RNA-guided Cas9 nucleases) system. Depletion of B. mori Torso (BmTorso) did not eventually affect larval ecdysis and metamorphosis processes. Instead, BmTorso deficiency resulted in significant extension of developing time during larval and pupal stages with increased pupa and cocoon sizes. The ecdysteriod titers in the hemolymph of BmTorso mutants sharpy declined. Transcriptional levels of genes involved in ecdysone biosynthesis and ecdysteroid signaling pathways were significantly reduced in BmTorso-deficient animals. Additionally, RNA-Seq analysis revealed that genes involved in the longevity pathway and protein processing in the endoplasmic reticulum pathway were affected after BmTorso deletion. These results indicate that Torso is critical for maintaining steroid hormone homeostasis in insects.

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“…The correct size at pupariation is monitored by the corpora allata, the production tissue of PTTH ( Mirth et al, 2005 ; Shimell et al, 2018 ). Furthermore, PTTH integrates light signaling and photo periods to coordinate developmental timing to circadian rhythms ( Mirth et al, 2005 ; Shimell et al, 2018 ) and forms a feed-forward loop with ecdysone signaling in the brain ( Christensen et al, 2020 ). ILPs do not only act through the PTTH axis to mediate their effect on the ecdysone but are able to directly control the ecdysone production in the prothoracic gland (PG) ( Colombani, 2005 ).…”

Section: Ecdysone Receptor Signalingmentioning

confidence: 99%

Function and Evolution of Nuclear Receptors in Environmental-Dependent Postembryonic Development

Taubenheim

Kortmann

Fraune

2021

Front. Cell Dev. Biol.

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Nuclear receptors (NRs) fulfill key roles in the coordination of postembryonal developmental transitions in animal species. They control the metamorphosis and sexual maturation in virtually all animals and by that the two main environmental-dependent developmental decision points. Sexual maturation and metamorphosis are controlled by steroid receptors and thyroid receptors, respectively in vertebrates, while both processes are orchestrated by the ecdysone receptor (EcR) in insects. The regulation of these processes depends on environmental factors like nutrition, temperature, or photoperiods and by that NRs form evolutionary conserved mediators of phenotypic plasticity. While the mechanism of action for metamorphosis and sexual maturation are well studied in model organisms, the evolution of these systems is not entirely understood and requires further investigation. We here review the current knowledge of NR involvement in metamorphosis and sexual maturation across the animal tree of life with special attention to environmental integration and evolution of the signaling mechanism. Furthermore, we compare commonalities and differences of the different signaling systems. Finally, we identify key gaps in our knowledge of NR evolution, which, if sufficiently investigated, would lead to an importantly improved understanding of the evolution of complex signaling systems, the evolution of life history decision points, and, ultimately, speciation events in the metazoan kingdom.

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Ecdysone-dependent feedback regulation of prothoracicotropic hormone controls the timing of developmental maturation

Cited by 20 publications

References 55 publications

Ecdysone acts through cortex glia to regulate sleep in Drosophila

Ecdysone acts through cortex glia to regulate sleep in Drosophila

The receptor tyrosine kinase torso regulates ecdysone homeostasis to control developmental timing in Bombyx mori

Function and Evolution of Nuclear Receptors in Environmental-Dependent Postembryonic Development

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