Expression of human genes in the fly eye reveals interaction with potential relevance to breast cancer

HumanaFly: high-throughput transgenesis and expression of breast cancer transcripts in Drosophila eye discovers the RPS12-Wingless signaling axis  

Katanaev, Kryuchkov, Averkov, Savitsky, Nikolaeva, Klimova, Khaustov & Solis  

Scientific Reports  (2020) vol. 10, no. 21013

 

Abstract: "Drosophila melanogaster has been a model for multiple human disease conditions, including cancer. Among Drosophila tissues, the eye development is particularly sensitive to perturbations of the embryonic signaling pathways, whose improper activation in humans underlies various forms of cancer. We have launched the HumanaFly project, whereas human genes expressed in breast cancer patients are screened for their ability to aberrate development of the Drosophila eye, hoping to thus identify novel oncogenes. Here we report identification of a breast cancer transgene, which upon expression in Drosophila produces eye malformation similar to the famous Glazed phenotype discovered by Thomas Morgan and decades later dissected to originate from mis-expression of Wingless (Wg). Wg is the ortholog of human Wnt proteins serving as ligands to initiate the developmental/oncogenic Wnt signaling pathway. Through genetic experiments we identified that this transgene interacted with the Wg production machinery, rather than with Wg signal transduction. In Drosophila imaginal discs, we directly show that the transgene promoted long-range diffusion of Wg, affecting expression of the Wg target genes. The transgene emerged to encode RPS12—a protein of the small ribosomal subunit overexpressed in several cancer types and known to also possess extra-ribosomal functions. Our work identifies RPS12 as an unexpected regulator of secretion and activity of Wnts. As Wnt signaling is particularly important in the context of breast cancer initiation and progression, RPS12 might be implicated in tumorigenesis in this and other Wnt-dependent cancers. Continuation of our HumanaFly project may bring further discoveries on oncogenic mechanisms."

An inexpensive method for modeling TBI in flies at different levels of severity

Saikumar J, Kim J, Byrns CN, Hemphill M, Meaney DF, Bonini NM. Inducing different severities of traumatic brain injury in Drosophila using a piezoelectric actuator. Nat Protoc. 2020 Dec 4. doi: 10.1038/s41596-020-00415-y. Epub ahead of print. PMID: 33277631.

Abstract:

"Drosophila models have been instrumental in providing insights into molecular mechanisms of neurodegeneration, with wide application to human disease. The brain degeneration associated with traumatic brain injury (TBI) has been modeled in Drosophila using devices that inflict trauma on multiple parts of the fly body, including the head. However, the injuries produced by these models are not specific in location and are inconsistent between individual animals. We have recently developed a device that can be used to inflict controlled head injury to flies, resulting in physiological responses that are remarkably similar to those observed in humans with TBI. This protocol describes the construction, calibration and use of the Drosophila TBI (dTBI) device, a platform that employs a piezoelectric actuator to reproducibly deliver a force in order to briefly compress the fly head against a metal surface. The extent of head compression can be controlled through an electrical circuit, allowing the operator to set different levels of injury. The entire device can be assembled and calibrated in under a week. The device components and the necessary electrical tools are readily available and cost ~$800. The dTBI device can be used to harness the power of Drosophila genetics and perform large-scale genetic or pharmacological screens, using a 7-d post-injury survival curve to identify modifiers of injury."