Thyroid hormones drive central nervous system remodelling during flatfish metamorphosis

Area of Science:

• Developmental Biology
• Endocrinology
• Neuroscience

Background:

• Flatfish metamorphosis involves significant craniofacial changes and CNS remodelling, largely driven by thyroid hormones (THs).
• The precise role of THs in the central nervous system (CNS) remodelling during flatfish metamorphosis is not fully understood.

Purpose of the Study:

• To investigate the role of THs in CNS remodelling during Solea senegalensis metamorphosis.
• To identify TH-regulated genes involved in CNS development and plasticity.

Main Methods:

• Integrated high-throughput transcriptomic analysis with experimental manipulation of TH levels using methimazole (MMI) or exogenous T4.
• Utilized cell proliferation assays and region-specific gene expression analyses.

Main Results:

• Identified 567 differentially expressed genes related to CNS development, neuronal/glial differentiation, migration, myelination, and metabolism.
• Observed down-regulation of key CNS factors (klf9, sox9, mbp, plp) in MMI-treated larvae and increased neural proliferation under hypothyroidism.
• Uncovered distinct patterns of TH signaling in head and body regions, highlighting spatial complexity.

Conclusions:

• THs are essential for both morphological transformation and CNS plasticity during flatfish metamorphosis.
• THs play a conserved role in vertebrate brain development, as evidenced by their impact on CNS remodelling in flatfish.