Embryonic exposure to 3,3’,5-triiodo-L-thyronine affects oligodendroglial lineage during neurodevelopment in zebrafish

Thyroid hormones (THs) regulate oligodendrogenesis and myelination in the developing central nervous system (CNS), particularly during the perinatal period when oligodendrocyte precursor cells (OPCs) differentiate into myelinating oligodendrocytes. However, whether THs influence earlier developmental stages, when neural progenitor cells (NPCs) commit to the oligodendroglial lineage, remains unclear. Here, we investigated the effects of increased embryonic 3,3’,5-triiodo-L-thyronine (T3) exposure on oligodendroglial development in zebrafish. T3 bioavailability was enhanced either by transient exogenous T3 exposure within the first 24 h post-fertilization or by disruption of the TH-inactivating deiodinase gene dio3b . Embryonic T3 exposure reduced myelin content in the entire brain and decreased the expression of oligodendroglial markers. These changes were preceded by increased expression of NPC proliferation markers and accompanied by elevated expression of a neuronal precursor marker, suggesting altered lineage commitment. In contrast, dio3b disruption produced temporally and regionally restricted effects, including increased OPC, myelin, and neuronal content in specific brain regions. Together, these findings suggest that TH availability during embryogenesis influences early lineage progression in the CNS and may contribute to the balance between neuronal and oligodendroglial development. Our results point to the embryonic stage as a sensitive period during which subtle TH fluctuations can affect oligodendrogenesis and myelination.