Ecdysone regulates Drosophila wing disc size via a TORC1 dependent mechanism.
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ABSTRACT:
SUBMITTER: Strassburger K
PROVIDER: S-EPMC8602387 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:While the membrane potential of cells has been shown to be patterned in some tissues, specific roles for membrane potential in regulating signalling pathways that function during development are still being established. In the Drosophila wing imaginal disc, Hedgehog (Hh) from posterior cells activates a signalling pathway in anterior cells near the boundary which is necessary for boundary maintenance. Here, we show that membrane potential is patterned in the wing disc. Anterior cells near the boundary, where Hh signalling is most active, are more depolarized than posterior cells across the boundary. Elevated expression of the ENaC channel Ripped Pocket (Rpk), observed in these anterior cells, requires Hh. Antagonizing Rpk reduces depolarization and Hh signal transduction. Using genetic and optogenetic manipulations, in both the wing disc and the salivary gland, we show that membrane depolarization promotes membrane localization of Smoothened and augments Hh signalling, independently of Patched. Thus, membrane depolarization and Hh-dependent signalling mutually reinforce each other in cells immediately anterior to the compartment boundary.
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Project description:The molecular mechanisms regulating tissue size represent an unsolved puzzle in developmental biology. One signalling pathway controlling growth of the Drosophila wing is Dpp. Dpp promotes growth by repression of the transcription factor Brk. The transcriptional targets of Brk that control cell growth and proliferation, however, are not yet fully elucidated. We report here a genome-wide ChIP-Seq of endogenous Brk from wing imaginal discs. We identify the growth regulator Myc as a target of Brk and show that repression of Myc and of the miRNA bantam explains a significant fraction of the growth inhibition caused by Brk. This work sheds light on the effector mechanisms by which Dpp signalling controls tissue growth.
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Project description:Imaginal disc development in Drosophila requires coordinated cellular proliferation and tissue patterning. In our studies of TGF? superfamily signaling components, we found that a protein null mutation of Smad2, the only Activin subfamily R-Smad in the fruit fly, produces overgrown wing discs that resemble gain of function for BMP subfamily signaling. The wing discs are expanded specifically along the anterior-posterior axis, with increased proliferation in lateral regions. The morphological defect is not observed in mutants for the TGF? receptor baboon, and epistasis tests showed that baboon is epistatic to Smad2 for disc overgrowth. Rescue experiments indicate that Baboon binding, but not canonical transcription factor activity, of Smad2 is required for normal disc growth. Smad2 mutant discs generate a P-Mad stripe that is narrower and sharper than the normal gradient, and activation targets are correspondingly expressed in narrowed domains. Repression targets of P-Mad are profoundly mis-regulated, with brinker and pentagone reporter expression eliminated in Smad2 mutants. Loss of expression requires a silencer element previously shown to be controlled by BMP signaling. Epistasis experiments show that Baboon, Mad and Schnurri are required to mediate the ectopic silencer output in the absence of Smad2. Taken together, our results show that loss of Smad2 permits promiscuous Baboon activity, which represses genes subject to control by Mad-dependent silencer elements. The absence of Brinker and Pentagone in Smad2 mutants explains the compound wing disc phenotype. Our results highlight the physiological relevance of substrate inhibition of a kinase, and reveal a novel interplay between the Activin and BMP pathways.
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Project description:The molecular mechanisms regulating tissue size represent an unsolved puzzle in developmental biology. One signaling pathway controlling growth of the Drosophila wing is Dpp. Dpp promotes growth via repression of the transcription factor Brinker. The transcriptional targets of Brinker that control cell growth and proliferation, however, are not yet fully elucidated. We report here a genome-wide ChIP-seq of endogenous Brinker from wing imaginal discs. We identify the growth regulator Myc as a target of Brinker and show that Myc together with the microRNA bantam explain a large fraction of the growth inhibition caused by Brinker. This work sheds light on the effector mechanisms by which Dpp signaling controls tissue growth. Identification of Brinker binding sites in Wing imaginal discs cells
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Project description:The wing of the fruit fly, Drosophila melanogaster, with its simple, two-dimensional structure, is a model organ well suited for a systems biology approach. The wing arises from an epithelial sac referred to as the wing imaginal disc, which undergoes a phase of massive growth and concomitant patterning during larval stages. The Decapentaplegic (Dpp) morphogen plays a central role in wing formation with its ability to co-coordinately regulate patterning and growth. Here, we asked whether the Dpp signaling activity scales, i.e. expands proportionally, with the growing wing imaginal disc. Using new methods for spatial and temporal quantification of Dpp activity and its scaling properties, we found that the Dpp response scales with the size of the growing tissue. Notably, scaling is not perfect at all positions in the field and the scaling of target gene domains is ensured specifically where they define vein positions. We also found that the target gene domains are not defined at constant concentration thresholds of the downstream Dpp activity gradients P-Mad and Brinker. Most interestingly, Pentagone, an important secreted feedback regulator of the pathway, plays a central role in scaling and acts as an expander of the Dpp gradient during disc growth.
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Project description:Sequential pulses of the steroid hormone ecdysone regulate the major developmental transitions in Drosophila, and the duration of each developmental stage is determined by the length of time between ecdysone pulses. Ecdysone regulates biological responses by directly initiating target gene transcription. In turn, these transcriptional responses are known to be self-limiting, with mechanisms in place to ensure regression of hormone-dependent transcription. However, the biological significance of these transcriptional repression mechanisms remains unclear. Here we show that the chromatin remodeling protein INO80 facilitates transcriptional repression of ecdysone-regulated genes during prepupal development. In ino80 mutant animals, inefficient repression of transcriptional responses to the late larval ecdysone pulse delays the onset of the subsequent prepupal ecdysone pulse, resulting in a significantly longer prepupal stage. Conversely, increased expression of ino80 is sufficient to shorten the prepupal stage by increasing the rate of transcriptional repression. Furthermore, we demonstrate that enhancing the rate of regression of the mid-prepupal competence factor ?FTZ-F1 is sufficient to determine the timing of head eversion and thus the duration of prepupal development. Although ino80 is conserved from yeast to humans, this study represents the first characterization of a bona fide ino80 mutation in any metazoan, raising the possibility that the functions of ino80 in transcriptional repression and developmental timing are evolutionarily conserved.
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Project description:The robust specification of organ development depends on coordinated cell-cell communication. This process requires signal integration among multiple pathways, relying on second messengers such as calcium ions. Calcium signaling encodes a significant portion of the cellular state by regulating transcription factors, enzymes, and cytoskeletal proteins. However, the relationships between the inputs specifying cell and organ development, calcium signaling dynamics, and final organ morphology are poorly understood. Here, we have designed a quantitative image-analysis pipeline for decoding organ-level calcium signaling. With this pipeline, we extracted spatiotemporal features of calcium signaling dynamics during the development of the Drosophila larval wing disc, a genetic model for organogenesis. We identified specific classes of wing phenotypes that resulted from calcium signaling pathway perturbations, including defects in gross morphology, vein differentiation, and overall size. We found four qualitative classes of calcium signaling activity. These classes can be ordered based on agonist stimulation strength Gαq-mediated signaling. In vivo calcium signaling dynamics depend on both receptor tyrosine kinase/phospholipase C γ and G protein-coupled receptor/phospholipase C β activities. We found that spatially patterned calcium dynamics correlate with known differential growth rates between anterior and posterior compartments. Integrated calcium signaling activity decreases with increasing tissue size, and it responds to morphogenetic perturbations that impact organ growth. Together, these findings define how calcium signaling dynamics integrate upstream inputs to mediate multiple response outputs in developing epithelial organs.
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Project description:Research on the ability of certain organisms to reconstruct missing structures of their bodies is still in its infancy, despite numerous efforts performed in multiple species. Using expression profile analyses on different timepoints that cover wound healing and regeneration processes (0, 24 and 72 hours post injury), we studied the regenerative behaviour of fragmented wing imaginal discs of D. melanogaster implanted into adult flies. First, through the comparison between cut and intact discs, we identified the effect of implantation on the regeneration process. Filtering this information, we then constructed the specific early regeneration gene signature of wing discs in which multiple transcription factors, immune response genes and members of the JNK, Notch and WNT signaling pathways seem to play an important role. We next compared the transcriptomes of discs 24 and 72 hours after fragmentation to characterize the regenerative machinery and observed a temporal decrease in the cellular metabolic processes, RNA processing and gene expression machinery, suggesting the discs normal activity was stopped on this first interval of time in response to injury and implantation offences. Based on the expression patterns, we elaborated a catalogue of genes involved in wing disc regeneration divided into four classes (wound healing, regeneration, quick response, constant response).
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Project description:The molecular mechanisms regulating tissue size represent an unsolved puzzle in developmental biology. One signaling pathway controlling growth of the Drosophila wing is Dpp. Dpp promotes growth via repression of the transcription factor Brinker. The transcriptional targets of Brinker that control cell growth and proliferation, however, are not yet fully elucidated. We report here a genome-wide ChIP-seq of endogenous Brinker from wing imaginal discs. We identify the growth regulator Myc as a target of Brinker and show that Myc together with the microRNA bantam explain a large fraction of the growth inhibition caused by Brinker. This work sheds light on the effector mechanisms by which Dpp signaling controls tissue growth.
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