Sequence environment of BMP-dependent <i>activating elements</i> controls transcriptional responses to Dpp signaling in <i>Drosophila</i>

Chayengia, Mrinal; Veikkolainen, Ville; Jevtic, Milica; Pyrowolakis, George

doi:10.1242/dev.176107

Cited by 6 publications

(6 citation statements)

References 54 publications

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“…Brk repression is known to be relieved by the activator protein Shn. 26 , 27 To determine that this transcriptional regulation system is present in the nociceptor, we used a line in which a GFP tag had been inserted in the C-terminus of the Shn reading frame using the P[acman] system. 33 The Shn tagged GFP line was crossed with a line expressing tdTomato under the control of the pickpocket promoter in the nociceptors and progeny were imaged using confocal microscopy.…”

Section: Resultsmentioning

confidence: 99%

“…After epidermal injury by ultraviolet light, cytokines are released from the epidermis onto underlying nociceptors 9 and presumably trigger Dpp release, which then binds its receptors on the nociceptors. 11 Dpp’s intracellular transducer molecules Mad and Med then enter the nucleus and there interact with Brk and Shn, with the effect of relieving repression by Brk, 26 , 27 effectively releasing the pathways’s target genes for transcription.…”

Section: Discussionmentioning

confidence: 99%

“…24,25 The Mad/Med complex is thought to recruit transcription regulator Shn that binds DNA and relieves Brk repression. 26,27 It is hypothesized, then, that since knockdown of Dpp produces failure to sensitize after injury, 11 knockdown of Shn may have the same effect, and knockdown of Brk may have an opposite effect, that is, hypersensitivity in the absence of injury.…”

Section: Introductionmentioning

confidence: 99%

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The brinker repressor system regulates injury-induced nociceptive sensitization in Drosophila melanogaster

et al. 2021

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Chronic pain is a debilitating condition affecting millions of people worldwide, and an improved understanding of the pathophysiology of chronic pain is urgently needed. Nociceptors are the sensory neurons that alert the nervous system to potentially harmful stimuli such as mechanical pressure or noxious thermal temperature. When an injury occurs, the nociceptive threshold for pain is reduced and an increased pain signal is produced. This process is called nociceptive sensitization. This sensitization normally subsides after the injury is healed. However, dysregulation can occur which results in sensitization that persists after the injury has healed. This process is thought to perpetuate chronic pain. The Hedgehog (Hh) signaling pathway has been previously implicated in nociceptive sensitization in response to injury in Drosophila melanogaster. Downstream of Hh signaling, the Bone Morphogenetic Protein (BMP) pathway has also been shown to be necessary for this process. Here, we describe a role for nuclear components of BMP’s signaling pathway in the formation of injury-induced nociceptive sensitization. Brinker (Brk), and Schnurri (Shn) were suppressed in nociceptors using an RNA-interference (RNAi) “knockdown” approach. Knockdown of Brk resulted in hypersensitivity in the absence of injury, indicating that it normally acts to suppress nociceptive sensitivity. Animals in which transcriptional activator Shn was knocked down in nociceptors failed to develop normal allodynia after ultraviolet irradiation injury, indicating that Shn normally acts to promote hypersensitivity after injury. These results indicate that Brk-related transcription regulators play a crucial role in the formation of nociceptive sensitization and may therefore represent valuable new targets for pain-relieving medications.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The brinker repressor system regulates injury-induced nociceptive sensitization in Drosophila melanogaster

et al. 2021

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“…GSCs in the niche secrete BMP ligands that promote the phosphorylation of Samd1/5/8 [ 46 ]. pSmad1/5/8 forms a complex with Smad4 to activate the promoter activity of stem cell maintenance factor Nos and differentiation factor Bam to increase the number of GSCs [ 47 , 48 ]. In this study, ginsenoside Rg1 activates ECR to increase BMP signal strength ( Figure 7 ).…”

Section: Discussionmentioning

confidence: 99%

New insights into ginsenoside Rg1 regulating the niche to inhibit age-induced germline stem cells depletion through targeting ECR/BMP signaling pathway in Drosophila

Fu,

Ma,

Liu

et al. 2024

Aging

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Purpose: The age-induced imbalance in ecological niches leads to the loss of GSCs, which is the main reason for ovarian germline senescence. Ginsenoside Rg1 can delay ovarian senescence. Here, we shed light on new insights of ginsenoside Rg1 in regulating the niche to maintain GSCs self-renewal and discussing related molecular mechanisms. Methods: The differences among GSC number, reproductive capacity of naturally aging female Drosophila after ginsenoside Rg1 feeding were analyzed by immunofluorescence and behavior monitoring. The expressions of the active factors in the niche and the BMP signaling were analyzed through Western blot and RT-qPCR. The target effect was verified in the ECR mutant and combined with the molecular docking. Results: Ginsenoside Rg1 inhibited the age-induced reduction of the GSCs number and restored offspring production and development. Ginsenoside Rg1 promoted the expression of anchor proteins E-cadherin, stemness maintenance factor Nos and differentiation promoting factor Bam, thereby GSCs niche homeostasis was regulated. In addition, ginsenoside Rg1 was bound to the LBD region of the hormone receptor ECR. Ginsenoside Rg1 promotes the regeneration of GSCs by targeting the ECR to increase pSmad1/5/8 expression and thereby activating the BMP signaling pathway. In addition, ginsenoside Rg1 maintenance of niche homeostasis to promote GSCs regeneration is dependent on ECR as demonstrated in ECR mutants. Conclusions: Ginsenoside Rg1 regulated the ecological niche homeostasis of GSCs and promoted the regeneration of GSCs by targeting the ECR/BMP signaling pathway in hormone-deficient states in aging ovaries. It is of great significance for prolonging fertility potential and delaying ovarian senescence.

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“…For genes examined in depth, either the responsiveness to BMP signaling or the complex pattern of signaling is a combinatorial response to multiple signaling pathways ( Liang et al . 2012 ; Chayengia et al . 2019 ).…”

Section: Regulation Of Bmp Signalingmentioning

confidence: 99%

Bone morphogenetic protein signaling: the pathway and its regulation

Akiyama,

Raftery,

Wharton

2023

Genetics

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In the mid-1960s, bone morphogenetic proteins (BMPs) were first identified in the extracts of bone to have the remarkable ability to induce heterotopic bone. When the Drosophila gene decapentaplegic (dpp) was first identified to share sequence similarity with mammalian BMP2/BMP4 in the late-1980s, it became clear that secreted BMP ligands can mediate processes other than bone formation. Following this discovery, collaborative efforts between Drosophila geneticists and mammalian biochemists made use of the strengths of their respective model systems to identify BMP signaling components and delineate the pathway. The ability to conduct genetic modifier screens in Drosophila with relative ease was critical in identifying the intracellular signal transducers for BMP signaling and the related transforming growth factor-beta/activin signaling pathway. Such screens also revealed a host of genes that encode other core signaling components and regulators of the pathway. In this review, we provide a historical account of this exciting time of gene discovery and discuss how the field has advanced over the past 30 years. We have learned that while the core BMP pathway is quite simple, composed of 3 components (ligand, receptor, and signal transducer), behind the versatility of this pathway lies multiple layers of regulation that ensures precise tissue-specific signaling output. We provide a sampling of these discoveries and highlight many questions that remain to be answered to fully understand the complexity of BMP signaling.

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Sequence environment of BMP-dependent activating elements controls transcriptional responses to Dpp signaling in Drosophila

Cited by 6 publications

References 54 publications

The brinker repressor system regulates injury-induced nociceptive sensitization in Drosophila melanogaster

The brinker repressor system regulates injury-induced nociceptive sensitization in Drosophila melanogaster

New insights into ginsenoside Rg1 regulating the niche to inhibit age-induced germline stem cells depletion through targeting ECR/BMP signaling pathway in Drosophila

Bone morphogenetic protein signaling: the pathway and its regulation

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