The developmental progression of eight opsin spectral signals recorded from the zebrafish retinal cone layer is altered by the timing and cell type expression of thyroxin receptor β2 (trβ2) gain-of-function transgenes

Abstract

Thyroid hormone receptor β2 (trβ2), a splice variant of thyroxin receptor β, is a transcription factor/nuclear receptor selectively expressed in vertebrate long-wavelength-sensitive (LWS/red) retinal cones and essential for LWS cone development. Using two gain-of-function zebrafish transgenics, we examine the physiological and morphological impact of excess trβ2 in zebrafish cone specification. The crx:mYFP-2A-trβ2 transgenic expresses trβ2 early, in retinal progenitors, while gnat2:mYFP-2A-trβ2;mpv17-/- expresses trβ2 later, in differentiated cone cells. Here electroretinographic signals are isolated from cones by synaptic blockade and the cone spectral composition analyzed. In 5-day crx:mYFP-2A-trβ2 embryos, UV- and blue-cone signals are attenuated while LWS2 (larval red-cone opsin) amplitudes increase. 5-day gnat2:mYFP-2A-trβ2;mpv17-/- spectra are indistinguishable from controls but LWS2 signals surpass controls during later embryonic and juvenile stages. By adulthood, both transgenics become entirely, or almost entirely, red cone dichromats, with LWS1 (adult red-cone opsin) amplitudes becoming super-normal, exceeding adult LWS2 signals, which are unchanged. Adult control LWS1 and LWS2 signal amplitudes are about equal. There are mixed opsin cones in both transgenic larvae. In gnat2:mYFP-2A-trβ2;mpv17-/-, mixed UV- red- opsin immunoreactive cones, a reporter for the UV opsin gene is suppressed, suggesting a UV-to-red cone transformation process. Larval cones with gain-of-function transgenes are morphologically distinct from red, blue or UV cones, with wider inner segments and shorter axons than red cones, suggesting both cone spectral specification and shape are influenced by trβ2.

Thyroid hormone as a temporal switch in mouse development

“…In particular zebrafish is a popular model which introduces a useful complement as it is ectotherm, has a high regeneration capacity and does not undergo an obvious metamorphosis. This model has not yet been fully exploited, and provide attractive models to analyze the developmental function of T3, notably in bones ( 65) skin (66,67) retina (68,69) and lateral line, which is a sensory organ which function is comparable to the one of the inner ear (70).…”