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Accelerated cell cycles enable organ regeneration under developmental time constraints in the Drosophila hindgut

View ORCID ProfileErez Cohen, View ORCID ProfileDonald T. Fox
doi: https://doi.org/10.1101/2020.02.17.953075
Erez Cohen
1Department of Cell Biology, Duke University School of Medicine, Durham, United States.
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Donald T. Fox
1Department of Cell Biology, Duke University School of Medicine, Durham, United States.
2Department of Pharmacology & Cancer Biology, Duke University School of Medicine, Durham, United States.
3Regeneration Next Initiative, Duke University School of Medicine, Durham, United States.
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  • For correspondence: don.fox@duke.edu
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Summary

Individual organ development must be temporally coordinated with development of the rest of the organism. As a result, cell division in a developing organ occurs on a relatively fixed time scale. Despite this, many developing organs can regenerate cells lost to injury. How organs regenerate within the time constraints of organism development remains unclear. Here, we show the developing Drosophila hindgut regenerates by accelerating the mitotic cell cycle. This process requires JAK/STAT signaling and is achieved by decreasing G1 length during the normal period of developmental mitoses. Mitotic capacity is then terminated by the steroid hormone ecdysone receptor. This receptor activates a hindgut-specific enhancer of fizzy-related, a negative regulator of mitotic cyclins. We further identify the Sox transcription factor Dichaete as an important negative regulator of injury-induced mitotic cycles. Our findings reveal how mitotic cell cycle entry mechanisms can be adapted to accomplish developmental organ regeneration.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted February 17, 2020.
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Accelerated cell cycles enable organ regeneration under developmental time constraints in the Drosophila hindgut
Erez Cohen, Donald T. Fox
bioRxiv 2020.02.17.953075; doi: https://doi.org/10.1101/2020.02.17.953075
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Accelerated cell cycles enable organ regeneration under developmental time constraints in the Drosophila hindgut
Erez Cohen, Donald T. Fox
bioRxiv 2020.02.17.953075; doi: https://doi.org/10.1101/2020.02.17.953075

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