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Compensatory proliferation in Drosophila imaginal discs requires Dronc-dependent p53 activity.

ABSTRACT: BACKGROUND:The p53 transcription factor directs a transcriptional program that determines whether a cell lives or dies after DNA damage. Animal survival after extensive cellular damage often requires that lost tissue be replaced through compensatory growth or regeneration. In Drosophila, damaged imaginal disc cells can induce the proliferation of neighboring viable cells, but how this is controlled is not clear. Here we provide evidence that Drosophila p53 (dp53) has a previously unidentified role in coordinating the compensatory growth response to tissue damage. RESULTS:We find that dp53, the sole p53 ortholog in Drosophila, is required for each component of the response to cellular damage, including two separate cell-cycle arrests, changes in patterning gene expression, cell proliferation, and growth. We demonstrate that these processes are regulated by dp53 in a manner that is independent of DNA-damage sensing but that requires the initiator caspase Dronc. Our results indicate that once induced, dp53 amplifies and sustains the response through a positive feedback loop with Dronc and the apoptosis-inducing factors Hid and Reaper. CONCLUSIONS:How cell death and cell proliferation are coordinated during development and after stress is a fundamental question that is critical for an understanding of growth regulation. Our data suggest that dp53 may carry out an ancestral function that promotes animal survival through the coordination of responses leading to compensatory growth after tissue damage.

SUBMITTER: Wells BS

PROVIDER: S-EPMC1764442 | biostudies-literature | 2006 Aug

REPOSITORIES: biostudies-literature

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Compensatory proliferation in Drosophila imaginal discs requires Dronc-dependent p53 activity.

Wells Brent S BS Yoshida Eri E Johnston Laura A LA

Current biology : CB 20060801 16

<h4>Background</h4>The p53 transcription factor directs a transcriptional program that determines whether a cell lives or dies after DNA damage. Animal survival after extensive cellular damage often requires that lost tissue be replaced through compensatory growth or regeneration. In Drosophila, damaged imaginal disc cells can induce the proliferation of neighboring viable cells, but how this is controlled is not clear. Here we provide evidence that Drosophila p53 (dp53) has a previously unident ...[more]

PMID: 16920621

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Project description:The wing imaginal disc of Drosophila melanogaster is a prominent experimental system for research on control of cell growth, proliferation and death, as well as on pattern formation and morphogenesis during organogenesis. The precise genetic methodology applicable in this system has facilitated conceptual advances of fundamental importance for developmental biology. Experimental accessibility and versatility would gain further if long term development of wing imaginal discs could be studied also in vitro. For example, culture systems would allow live imaging with maximal temporal and spatial resolution. However, as clearly demonstrated here, standard culture methods result in a rapid cell proliferation arrest within hours of cultivation of dissected wing imaginal discs. Analysis with established markers for cells in S- and M phase, as well as with RGB cell cycle tracker, a novel reporter transgene, revealed that in vitro cultivation interferes with cell cycle progression throughout interphase and not just exclusively during G1. Moreover, quantification of EGFP expression from an inducible transgene revealed rapid adverse effects of disc culture on basic cellular functions beyond cell cycle progression. Disc transplantation experiments confirmed that these detrimental consequences do not reflect fatal damage of imaginal discs during isolation, arguing clearly for a medium insufficiency. Alternative culture media were evaluated, including hemolymph, which surrounds imaginal discs during growth in situ. But isolated larval hemolymph was found to be even less adequate than current culture media, presumably as a result of conversion processes during hemolymph isolation or disc culture. The significance of prominent growth-regulating pathways during disc culture was analyzed, as well as effects of insulin and disc co-culture with larval tissues as potential sources of endocrine factors. Based on our analyses, we developed a culture protocol that prolongs cell proliferation in cultured discs.

Dataset Information

Compensatory proliferation in Drosophila imaginal discs requires Dronc-dependent p53 activity.

Publications

Compensatory proliferation in Drosophila imaginal discs requires Dronc-dependent p53 activity.

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