Biology subjects

Losick, V. P.

Publications and source records attributed to Losick, V. P..

4 recordsLinked to original sources

bioRxiv2026

A genetic model of copulatory wounding in Drosophila melanogaster

In the animal kingdom, copulatory wounds occur due to aggressive behavior or injury from the female or male appendages in contact. Copulatory wounds are a source of sexual conflict as the injury can lead to death or infection. In the laboratory, Drosophila melanogaster does not ordinarily exhibit signs of injury during copulation, but here we find can be induced to do so by overexpression of the serine protease, Hayan, in either the male or female fruit fly. Melanin deposits mark sites of injury along the female ventral abdomen and occur following a single copulation event. The male fly mid-legs are the source of injury as they rub against the ventral female abdomen. Surgical removal of the male mid-legs prevents melanization while still permitting mating to occur. Likewise, removal of the right or left mid-leg results in a corresponding loss of melanization on the female abdominal side that lacks the mid-leg contact. Thus, it appears that overexpression of Hayan alters the female and male anatomy to sensitize it to injury during copulation. We show that these copulatory wounds heal similar to a puncture wound via the generation of enlarged multinucleated, polyploid cells. However, the size of the injury dictates the mechanism of healing. The polyploid cells arise solely by cell fusion in response to small injuries (<1,000m2), whereas the endocycle is simultaneously simulated by larger wounds (>3,000m2) to compensate for cell loss. Therefore, we speculate that wound-induced polyploidization may have evolved to repair similar injuries resulting from sexual conflict in nature.

developmental biology↗

bioRxiv2025

Epithelial cell fusion is required for tissue repair following UV-A irradiation

Cell cycle-dependent and independent mechanisms lead to the generation of mononucleated and multinucleated, polyploid cells. The more than doubling of a cells nuclear genome by endoreplication has been found to be an adaptation to genotoxic stress, enabling cell survival despite DNA damage. However, it remains unknown whether cells that increase ploidy via multinucleation also arise in response to genotoxic stress. Here, we use ultraviolet light A (UV-A) to induce permanent DNA damage in cells within the adult fruit fly epithelium. UV-A irradiation causes an injury-like response where giant multinucleated, polyploid cells arise following cell death. The epithelial cells undergo endoreplication, which is required to restore tissue mass, but is surprisingly dispensable for tissue repair. UV-A irradiation also induces cell fusion, which generates multinucleated cells that encompass almost the entire epithelial area post injury. Cell fusion can be inhibited by expression of a dominant negative Rac or Cdc42 GTPase, which then blocks epithelial tissue repair post irradiation. Apoptotic nuclei were detected at the site of cell junction breakdown suggesting that apoptosis itself or an apoptotic signal is required for polyploidization in this model. Expression of the effector caspase inhibitor, p35, led to inhibition of apoptosis, the endocycle, and cell fusion post UV-A. Therefore, we have discovered that caspase activation is necessary for polyploidization post injury and enhancing cell ploidy via multinucleation is another strategy to enable cell survival and tissue repair following genotoxic stress. Significance StatementPolyploid cells are lifes stress responders as the more than doubling of a cells genome has been shown to enable resistance to genotoxic stress. Cells are exposed to various sources of genotoxic stress, including from ultraviolet light. Here we find that ultraviolet light induces DNA damage causing apoptosis and the subsequent generation of giant, multinucleated polyploid cells in the fruit fly epithelium. Unlike in other models studied to date, cell fusion is the predominant response to genotoxic stress and appears to be essential for tissue repair. This study also determines that polyploidization post UV stress is dependent on caspase activation, suggesting a conserved mechanism to initiate cellular multinucleation both in development as well as in response to lifes stressors.

cell biology↗

bioRxiv2021

Blocking cell fusion inhibits age-induced polyploidy and maintains epithelial organization in Drosophila

A characteristic of normal aging and age-related diseases is the remodeling of a tissues cellular organization through polyploid cell growth. Polyploidy arises from an increase in nuclear ploidy or the number of nuclei per cell. However, it is not known whether age-induced polyploidy is an adaption to stressors or a precursor to degeneration. Here, we find that the adult fruit flys abdominal epithelium becomes polyploid with age through generation of large multinucleated cells that make up more than 40% of the tissue area. The syncytia arise by cell fusion, not endomitosis. Epithelial multinucleation is also a characteristic of macular degeneration, including Ctnna1tvrm5, a mouse model for pattern dystrophy. Similarly, we find that the knockdown of alpha-catenin enhances multinucleation in the fly epithelium. We further show that age-induced polyploidy can be suppressed by inhibiting cell fusion revealing a means to maintain tissue organization in older animals.

cell biology↗

bioRxiv2018

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

Tissue repair requires either polyploid cell growth or cell division, but the molecular mechanism promoting polyploidy and limiting proliferation 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, e2f1, or cycE). Myc is even sufficient to induce the endocycle in the 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 mitotic activator, Stg, while genetically depleting 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.

cell biology↗