Wound-induced polyploidization is driven by Myc and supports tissue repair in the presence of DNA damage

Janelle Grendler; Sara Lowgren; Monique Mills; Vicki P. Losick

doi:10.1242/dev.173005

journal article Open Access Aug 01, 2019

Wound-induced polyploidization is driven by Myc and supports tissue repair in the presence of DNA damage

Janelle Grendler Sara Lowgren Monique Mills Vicki P. Losick

Development Vol. 146 No. 15 · The Company of Biologists

View at Publisher Save 10.1242/dev.173005

Abstract

ABSTRACT
Tissue repair usually requires either polyploid cell growth or cell division, but the molecular mechanism promoting polyploidy and limiting cell division remains poorly understood. Here, we find that injury to the adult Drosophila epithelium causes cells to enter the endocycle through the activation of Yorkie-dependent genes (Myc and E2f1). Myc is even sufficient to induce the endocycle in the uninjured post-mitotic epithelium. As result, epithelial cells enter S phase but mitosis is blocked by inhibition of mitotic gene expression. The mitotic cell cycle program can be activated by simultaneously expressing the Cdc25-like phosphatase String (stg), while genetically depleting APC/C E3 ligase fizzy-related (fzr). However, forcing cells to undergo mitosis is detrimental to wound repair as the adult fly epithelium accumulates DNA damage, and mitotic errors ensue when cells are forced to proliferate. In conclusion, we find that wound-induced polyploidization enables tissue repair when cell division is not a viable option.

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Citations

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References

Details

Published: Aug 01, 2019
Vol/Issue: 146(15)
License: View

Authors

J

Janelle Grendler

Kathryn W. Davis Center for Regenerative Biology and Medicine , MDI Biological Laboratory, 159 Old Bar Harbor Rd, Bar Harbor, ME 04609 , USA

S

Sara Lowgren

Kathryn W. Davis Center for Regenerative Biology and Medicine , MDI Biological Laboratory, 159 Old Bar Harbor Rd, Bar Harbor, ME 04609 , USA

M

Monique Mills

Kathryn W. Davis Center for Regenerative Biology and Medicine , MDI Biological Laboratory, 159 Old Bar Harbor Rd, Bar Harbor, ME 04609 , USA

V

Vicki P. Losick

Kathryn W. Davis Center for Regenerative Biology and Medicine , MDI Biological Laboratory, 159 Old Bar Harbor Rd, Bar Harbor, ME 04609 , USA

Funding

National Institutes of Health Award: R35GM124691

National Institute of General Medical Sciences Award: P20GM104318

Cite This Article

Janelle Grendler, Sara Lowgren, Monique Mills, et al. (2019). Wound-induced polyploidization is driven by Myc and supports tissue repair in the presence of DNA damage. Development, 146(15). https://doi.org/10.1242/dev.173005

Wound-induced polyploidization is driven by Myc and supports tissue repair in the presence of DNA damage

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