Investigation of epitranscriptomic regulation in Scribble-mediated epithelial polarity disruption during Drosophila eye development

Abstract

Understanding epithelial tissue homeostasis is critical in animal development and disease, with apicobasal polarity (ABP) as a key regulatory mechanism. The ABP determinants, such as Scribble, also function as tumour suppressors, yet their role in growth regulation remains incompletely understood. N⁶-methyladenosine (m⁶A), an epitranscriptomic RNA modification mediated by Mettl3, has recently been implicated in gene regulation during cancer progression, but its role in polarity-loss-driven tumorigenesis is unclear. This study uses the Drosophila compound eye to investigate how altered Mettl3 activity influences tumour progression in scrib mutant cells. Using MARCM-based eyFLP mosaic analysis, scrib mutant clones with Mettl3 knockdown or overexpression were generated, and ommatidial disruption was quantified to assess tissue integrity. Altered Mettl3 expression increased tissue disruption, indicating that m⁶A acts as a modifier of ABP driven morphogenesis.