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Overexpression of Drosophila TET Causes Eye Development Abnormalities, Affecting Retinal Determination and Pathway Regulation

ABSTRACT: The discovery of somatic recurrent driver mutations in Histone H3.3 has profoundly revolutionized our understanding of high-grade gliomas (HGG) in children. Mutations in H3.3K27M and H3.3K36M disrupt normal gene regulation associated with eye development, piRNA biogenesis primarily through transposable element derepression. The regulation of transposable elements (TEs) is intricately linked to DNA methylation, particularly in mammalian models. This regulatory process is orchestrated through the interplay of key molecular players, namely the ten-eleven translocation (TET) proteins and DNA methyltransferases. We aim in this study to elucidate the interplay between mammalian TET2 and endogenous Drosophila Tet (dTet) concerning the H3.3K27M -induced eye phenotypes. Our findings demonstrate that the co-expression of the mTET2 R43G (non-catalytic) mutant with H3.3K27M amplifies the eye overgrowth phenotypes. Furthermore, the overexpression of dTet exacerbates the eye phenotype irrespective of H3.3K27M expression. Interestingly, overexpression of dTet upregulates wingless (wg); a key regulator in the Wnt signaling pathway and eye development, potentially repressing essential transcription factors required for eye specification resulting in the complete loss of eyes. Our results identify a novel role of dTet in the early stages of eye development, elucidating its impact on both retinal determination and wingless signaling pathways, which collectively regulate eye growth and differentiation.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE278796 | GEO | 2026/07/16

REPOSITORIES: GEO

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