During
            <i>Drosophila</i>
            disc regeneration, JAK/STAT coordinates cell proliferation with Dilp8-mediated developmental delay

Katsuyama, Tomonori; Comoglio, Federico; Seimiya, Makiko; Cabuy, Erik; Paro, Renato

doi:10.1073/pnas.1423074112

Cited by 108 publications

(161 citation statements)

References 50 publications

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“…S8F). While a recent study links Ilp8-expression to JAK/STAT signalling (Katsuyama et al, 2015), our data implies that Ilp8 is not a direct target gene of STAT92E. Instead, we suggest that cells that normally express Ilp8 in response to JNK activation are more likely to die when JAK/ STAT signalling is reduced, thereby preventing efficient expression of Ilp8 and induction of a developmental delay.…”

Section: Jak/stat Activity Promotes Efficient Induction Of Compensatocontrasting

confidence: 68%

JAK/STAT signalling mediates cell survival in response to tissue stress

et al. 2016

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Tissue homeostasis relies on the ability of tissues to respond to stress. Tissue regeneration and tumour models in Drosophila have shown that c-Jun amino-terminal kinase (JNK) acts as a prominent stress-response pathway promoting injury-induced apoptosis and compensatory proliferation. A central question remaining unanswered is how both responses are balanced by activation of a single pathway. Signalling through the Janus kinase/Signal transducers and activators of transcription (JAK/STAT) pathway, which is a potential JNK target, is implicated in promoting compensatory proliferation. While we observe JAK/STAT activation in imaginal discs upon damage, our data demonstrate that JAK/STAT and its downstream effector Zfh2 promote the survival of JNK signalling cells. The JNK component fos and the pro-apoptotic gene hid are regulated in a JAK/STAT-dependent manner. This molecular pathway restrains JNK-induced apoptosis and spatial propagation of JNK signalling, thereby limiting the extent of tissue damage, as well as facilitating systemic and proliferative responses to injury. We find that the pro-survival function of JAK/STAT also drives tumour growth under conditions of chronic stress. Our study defines the function of JAK/STAT in tissue stress and illustrates how crosstalk between conserved signalling pathways establishes an intricate equilibrium between proliferation, apoptosis and survival to restore tissue homeostasis.

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Section: Jak/stat Activity Promotes Efficient Induction Of Compensatocontrasting

confidence: 68%

JAK/STAT signalling mediates cell survival in response to tissue stress

et al. 2016

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“…JNK signaling is reduced in trx/+ mutants Previous reports have suggested that JNK signaling regulates dilp8 expression (Colombani et al, 2012;Katsuyama et al, 2015). Indeed, examination of the dilp8 locus in GenomeSurveyor (Kazemian et al, 2011) shows conservation of a predicted AP-1 binding site (Perkins et al, 1988) about 4 kb upstream of the dilp8 (CG14059) start site.…”

Section: E2mentioning

confidence: 96%

Trithorax regulates systemic signaling duringDrosophilaimaginal disc regeneration

2015

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Although tissue regeneration has been studied in a variety of organisms, from Hydra to humans, many of the genes that regulate the ability of each animal to regenerate remain unknown. The larval imaginal discs of the genetically tractable model organism Drosophila melanogaster have complex patterning, wellcharacterized development and a high regenerative capacity, and are thus an excellent model system for studying mechanisms that regulate regeneration. To identify genes that are important for wound healing and tissue repair, we have carried out a genetic screen for mutations that impair regeneration in the wing imaginal disc. Through this screen we identified the chromatin-modification gene trithorax as a key regeneration gene. Here we show that animals heterozygous for trithorax are unable to maintain activation of a developmental checkpoint that allows regeneration to occur. This defect is likely to be caused by abnormally high expression of puckered, a negative regulator of Jun N-terminal kinase (JNK) signaling, at the wound site. Insufficient JNK signaling leads to insufficient expression of an insulin-like peptide, dILP8, which is required for the developmental checkpoint. Thus, trithorax regulates regeneration signaling and capacity.

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“…Whether JAK/STAT is directly required for cell fusion during muscle development is unknown. JAK/STAT pathway activation is also crucial for regenerative cell proliferation in the Drosophila midgut and the mammalian liver (Sun and Irvine, 2014;Katsuyama et al, 2015), but whether the pathway has different roles in non-proliferative tissues during wound healing and regeneration is not known.…”

Section: Introductionmentioning

confidence: 99%

Spatiotemporal regulation of cell fusion by JNK and JAK/STAT signaling during Drosophila wound healing

Lee¹,

Lee²,

Park³

et al. 2017

Development

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Cell-cell fusion is widely observed during development and disease, and imposes a dramatic change on participating cells. Cell fusion should be tightly controlled, but the underlying mechanism is poorly understood. Here, we found that the JAK/STAT pathway suppressed cell fusion during wound healing in the Drosophila larval epidermis, restricting cell fusion to the vicinity of the wound. In the absence of JAK/STAT signaling, a large syncytium containing a 3-fold higher number of nuclei than observed in wild-type tissue formed in wounded epidermis. The JAK/STAT ligand-encoding genes upd2 and upd3 were transcriptionally induced by wounding, and were required for suppressing excess cell fusion. JNK (also known as Basket in flies) was activated in the wound vicinity and activity peaked at ∼8 h after injury, whereas JAK/STAT signaling was activated in an adjoining concentric ring and activity peaked at a later stage. Cell fusion occurred primarily in the wound vicinity, where JAK/STAT activation was suppressed by fusion-inducing JNK signaling. JAK/ STAT signaling was both necessary and sufficient for the induction of βPS integrin (also known as Myospheroid) expression, suggesting that the suppression of cell fusion was mediated at least in part by integrin protein.

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During Drosophila disc regeneration, JAK/STAT coordinates cell proliferation with Dilp8-mediated developmental delay

Cited by 108 publications

References 50 publications

JAK/STAT signalling mediates cell survival in response to tissue stress

JAK/STAT signalling mediates cell survival in response to tissue stress

Trithorax regulates systemic signaling duringDrosophilaimaginal disc regeneration

Spatiotemporal regulation of cell fusion by JNK and JAK/STAT signaling during Drosophila wound healing

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