Ets21C sustains a pro-regenerative transcriptional program in blastema cells of Drosophila imaginal discs

Worley, Melanie I.; Everetts, Nicholas J.; Yasutomi, Riku; Chang, Rebecca J; Saretha, Shrey; Yosef, Nir; Hariharan, Iswar K.

doi:10.1016/j.cub.2022.06.040

Cited by 17 publications

(26 citation statements)

References 79 publications

(129 reference statements)

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“…Combined, we find that JAK/STAT activity and Myc expression are specifically detected in cells undergoing compensatory proliferation that must be driven by non-autonomous signaling from egr- expressing domains. Indeed, JAK/STAT-activating, secreted ligands of the Unpaired family are expressed in JNK-signaling cells [ 41 , 42 , 52 , 58 – 60 ].…”

Section: Resultsmentioning

confidence: 99%

“…This drives apoptosis, but also disrupts overall tissue architecture, junctional integrity and epithelial polarity ( Fig 2A–2G , also compare Fig 3A–3C ) [ 33 , 35 ]. Due to the high activation of a JNK-dependent stress response program, egr- expression reproduces many hallmarks of highly inflammatory wounds [ 35 , 41 , 52 ]. Nevertheless, egr- expressing discs undergo compensatory proliferation to regenerate the damage [ 33 – 35 ].…”

Section: Resultsmentioning

confidence: 99%

“…signaling from egr-expressing domains. Indeed, JAK/STAT-activating, secreted ligands of the Unpaired family are expressed in JNK-signaling cells [41,42,52,[58][59][60].…”

Section: Jak/stat Signaling and Myc-expression Are Elevated In Prolif...mentioning

confidence: 99%

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Distinct signaling signatures drive compensatory proliferation via S-phase acceleration

et al. 2022

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Regeneration relies on cell proliferation to restore damaged tissues. Multiple signaling pathways activated by local or paracrine cues have been identified to promote regenerative proliferation. How different types of tissue damage may activate distinct signaling pathways and how these differences converge on regenerative proliferation is less well defined. To better understand how tissue damage and proliferative signals are integrated during regeneration, we investigate models of compensatory proliferation in Drosophila imaginal discs. We find that compensatory proliferation is associated with a unique cell cycle profile, which is characterized by short G1 and G2 phases and, surprisingly, by acceleration of the S-phase. S-phase acceleration can be induced by two distinct signaling signatures, aligning with inflammatory and non-inflammatory tissue damage. Specifically, non-autonomous activation of JAK/STAT and Myc in response to inflammatory damage, or local activation of Ras/ERK and Hippo/Yki in response to elevated cell death, promote accelerated nucleotide incorporation during S-phase. This previously unappreciated convergence of different damaging insults on the same regenerative cell cycle program reconciles previous conflicting observations on proliferative signaling in different tissue regeneration and tumor models.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Distinct signaling signatures drive compensatory proliferation via S-phase acceleration

et al. 2022

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“…The transcriptional signature downstream of the damage response includes the program for regenerative proliferation and repatterning ( Vizcaya-Molina et al, 2018 ; Harris et al, 2020 ; Worley et al, 2022 ) and the identification of the blastema signature ( Worley et al, 2022 ). In addition, JNK and p38 MAP kinases target the unpaired (Upd) cytokines (the Drosophila members of the interleukin-6 family), which are capable of activating the JAK/STAT pathway for growth control ( Pastor-Pareja et al, 2008 ; Jiang et al, 2009 ; Diaz-Garcia and Baonza, 2013 ; Katsuyama et al, 2015 ; Santabárbara-Ruiz et al, 2015 ; la Fortezza et al, 2016 ; Verghese and Su, 2016 ; Ahmed-de-Prado et al, 2018 ; Worley et al, 2018 ; Patel et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, JNK and p38 MAP kinases target the unpaired (Upd) cytokines (the Drosophila members of the interleukin-6 family), which are capable of activating the JAK/STAT pathway for growth control ( Pastor-Pareja et al, 2008 ; Jiang et al, 2009 ; Diaz-Garcia and Baonza, 2013 ; Katsuyama et al, 2015 ; Santabárbara-Ruiz et al, 2015 ; la Fortezza et al, 2016 ; Verghese and Su, 2016 ; Ahmed-de-Prado et al, 2018 ; Worley et al, 2018 ; Patel et al, 2019 ). Also, non-apoptotic JNK activity in regeneration is driven by, for example, Wg/Wnt signaling ( Smith-Bolton et al, 2009 ; Harris et al, 2016 ; Gracia-Latorre et al, 2022 ), Hippo signaling ( Grusche et al, 2011 ; Sun and Irvine, 2011 ; Repiso et al, 2013 ; Meserve and Duronio, 2015 ; Ruiz-Romero et al, 2015 ), Gadd45 , involved in DNA repair ( Camilleri-Robles et al, 2019 ), and Ets21c , a JNK-dependent transcription factor key for disc blastema cells ( Worley et al, 2022 ). Further research will be necessary to clarify whether the genetic response to JNK and p38 differs.…”

Section: Discussionmentioning

confidence: 99%

The sooner, the better: ROS, kinases and nutrients at the onset of the damage response in Drosophila

Serras

2022

Front. Cell Dev. Biol.

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One of the main topics in regeneration biology is the nature of the early signals that trigger the damage response. Recent advances in Drosophila point to the MAP3 kinase Ask1 as a molecular hub that integrates several signals at the onset of regeneration. It has been discovered that reactive oxygen species (ROS) produced in damaged imaginal discs and gut epithelia will activate the MAP3 kinase Ask1. Severely damaged and apoptotic cells produce an enormous amount of ROS, which ensures their elimination by activating Ask1 and in turn the pro-apoptotic function of JNK. However, this creates an oxidative stress environment with beneficial effects that is sensed by neighboring healthy cells. This environment, in addition to the Pi3K/Akt nutrient sensing pathway, can be integrated into Ask1 to launch regeneration. Ultimately the activity of Ask1 depends on these and other inputs and modulates its signaling to achieve moderate levels of p38 and low JNK signaling and thus promote survival and regeneration. This model based on the dual function of Ask1 for early response to damage is discussed here.

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Neural dependency in wound healing and regeneration

Noble,

Qubrosi,

Cariba

et al. 2023

Developmental Dynamics

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In response to injury, humans and many other mammals form a fibrous scar that lacks the structure and function of the original tissue, whereas other vertebrate species can spontaneously regenerate damaged tissues and structures. Peripheral nerves have been identified as essential mediators of wound healing and regeneration in both mammalian and nonmammalian systems, interacting with the milieu of cells and biochemical signals present in the post‐injury microenvironment. This review examines the diverse functions of peripheral nerves in tissue repair and regeneration, specifically during the processes of wound healing, blastema formation, and organ repair. We compare available evidence in mammalian and nonmammalian models, identifying critical nerve‐mediated mechanisms for regeneration and providing future perspectives toward integrating these mechanisms into a therapeutic framework to promote regeneration.

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Ets21C sustains a pro-regenerative transcriptional program in blastema cells of Drosophila imaginal discs

Cited by 17 publications

References 79 publications

Distinct signaling signatures drive compensatory proliferation via S-phase acceleration

Distinct signaling signatures drive compensatory proliferation via S-phase acceleration

The sooner, the better: ROS, kinases and nutrients at the onset of the damage response in Drosophila

Neural dependency in wound healing and regeneration

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