Chinmo defines the region-specific oncogenic competence in the Drosophila central nervous system
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While genetic mutations can promote hyperplastic growth, they do not always result in oncogenic outcomes. We and others have previously identified the transcription factors Nerfin-1 and Lola as inhibitors of dedifferentiation. Here, we investigate how the oncogenic potential of dedifferentiation varies across different neural lineages in the Drosophila central nervous system (CNS). We found that Nerfin-1 inactivation causes tumorigenic phenotypes in the central brain (CB) and the ventral nerve cord (VNC) but not the optic lobes (OLs). In contrast, Lola inactivation leads to tumour overgrowth specifically in the OLs. We identify Chinmo, a temporal transcription factor, and its regulation by ecdysone signalling as key determinants of the oncogenic competence in different regions of the brain, influencing the tumorigenic outcome of dedifferentiation. This work provides a fundamental framework to understand how oncogenic competence arises beyond genetic mutations.
Significance statement
In the CNS, the same tumorigenic mutation has been shown cause differential oncogenic outcomes in different regions of the brain. The mechanism underlying this phenomenon remains largely unknown. We have previously demonstrated that malignant brain tumours can be induced via neuronal dedifferentiation in the Drosophila CNS. Here, we demonstrate that dedifferentiated neural stem cells drive tumorigenesis in a region-specific manner, accounted for by region-specific expression and regulation of temporal factors by cell-intrinsic and hormonal signals. Together, this work extends our understandings of how brain regionalisation can be a constraint to oncogenesis.
