Drosophila eye development is compromised by dTet overexpression through altered retinal determination gene...

Epigenetic regulation via DNA demethylation and histone modification is essential for tissue development. We investigated the role of the Drosophila ten-eleven translocation protein (dTet) in eye development and its interaction with the oncohistone H3.3K27M. dTet overexpression in eye imaginal discs caused strong downregulation of retinal determination genes (toy, ey, so, eya, dac) and developmental arrest, leading to partial or complete eye loss. Enhanced dTet knockdown using sensitized conditions also resulted in eye developmental defects, supporting a dosage-dependent role for dTet during retinal morphogenesis. DNA-binding analysis using published ChIP-seq data revealed that dTet binds the promoters of these genes as well as wingless (wg), a negative regulator of eye specification, explaining its dual role in repressing retinal programs and activating Wnt/Wg signaling. Co-expression with H3.3K27M suppressed the mutation-induced overgrowth phenotype, whereas dTet loss enhanced it, indicating context-dependent modulation of tissue growth. Many dTet targets have conserved human orthologs implicated in congenital eye disorders, highlighting evolutionary conservation and potential translational relevance. These findings establish dTet as an important regulator of eye development.