Introduction: As in humans, thyroid hormone (TH) plays an essential role on zebrafish development by acting through the specific nuclear receptors (TRα or TRβ) and activating/suppressing the expression of several target genes. In zebrafish, TRα is preferentially expressed in the heart and CNS while the TRβ is mainly expressed in the retina and inner ear, but the specific role of these receptors in the different target tissues is presently unknown. In this study, we tested the role of TH and TRs during Zebrafish development and a particular attention has been devoted to the examination of the following target tissues brain, heart, sensory organs (retina and otoliths).
Methodology: Selvatic and transgenic zebrafish lines are injected with morpholinos, to knockdown the expression of the TRs and producing two different defective lines, MOs_TRα and MOs_TRβ. The morphological and functional anomalies of MOs_TRs were compared with MOs_ctrl at several time-points using different techniques: whole mount in situ hybridization, immunohistochemistry, histologic sections and confocal microscopy.
Results: Both defective morphant-fish lines display a series of growth alterations that depend on the type of defective-receptor and the preferential expression of the TR at tissue-level. i) Brain development: MOs_TRα show a severe cerebral hypoplasia and edema that impairs the proper CNS formation, while MOs_TRβ are quite comparable with controls. ii) Cardiac function: both MOs lines show structural and functional alterations compared to MOs_ctrl. MOs_TRα heart is heavily hypotrophic and bradycardic whilst MOs_TRβ are hypertrophic and tachycardic. iii) Sensory organs: only MOs_TRβ display severe abnormalities both in photoreceptors and otoliths (corresponding to the mammal innear ear) formation.
Discussion: Zebrafish is an excellent model to study the role of THs and TRs during embryonic development, representing an interesting and new biotool to test human TRα and TRβ mutations.