DNA methylation dynamics in ocular migration and visualadaptation

Third International Symposium on Epigenetics in Marine and Aquatic Research (EPIMAR2025), Barcelona, Spain, 27-30 May, 2025

The metamorphosis in flatfish is characterized by extensive tissue remodeling, encompassing alterations andadaptations associated with a transition from a pelagic to a benthic lifestyle. Among the most drastic anatomicaltransformations, is the migration from one eye to the opposite side of the body. This complex process involveschanges in the expression of many genes in different tissues, and therefore depends on the precisetranscriptional regulation of these genes. Epigenetic mechanisms, particularly DNA methylation, exert a pivotalinfluence on gene expression and play a crucial role in developmental programs. This study aimed to investigatethe DNA methylation profiles of migrating and non-migrating eyes using reduced-representation bisulfitesequencing (RRBS) during three key stages of turbot metamorphic process: pre-metamorphosis, climax and post-metamorphosis. A considerable number of hypermethylated regions, over 31% of all identified regions, werespecifically associated with the climax stage in both eyes, coinciding with elevated expression of the dnmt3agene, which is responsible for de novo methylation. We also observed at this stage alterations in expression ofphotoreceptor-specific genes involved in visual adaptation. Additionally, transcription factors crucial for retinalganglion cell (RGC) development, including the eomesa and tbr1b genes, exhibited differential methylation andexpression between the migrating and non-migrating eye during the climax phase. These findings underscorethe significance of DNA methylation in the intricate remodeling of the visual system during turbotmetamorphosis, particularly with regard to RGC-mediated ocular migration and the transmission of visualsignals. Overall, this study provides novel insights into the epigenetic regulation of the adaptive developmentalprocess in vertebrates

Funded by the Spanish Economy and Competitiveness Ministry project number AGL2014-52473R JR. L. Guerrero-Peña was supported by a pre-doctoral fellowship of the Spanish FPI Research Training Program grant number (PRE2018-085475)

Peer reviewed