A thyroid hormone receptor that is required for the development of green cone photoreceptors
Abstract. Color
vision is facilitated by distinct populations of cone photoreceptors in
the retina. In rodents, cones expressing different opsin photopigments
are sensitive to middle (M, 'green') and short (S, 'blue') wavelengths,
and are differentially distributed across the retina1,2. The mechanisms that control which opsin is expressed in a particular cone are poorly understood2,3, but previous in vitro studies implicated thyroid hormone in cone differentiation4,5.
Thyroid hormone receptor β2 (TRβ2) is a ligand-activated transcription
factor that is expressed in the outer nuclear layer of the embryonic
retina6,7. Here we delete Thrb
(encoding Trβ2) in mice, causing the selective loss of M-cones and a
concomitant increase in S-opsin immunoreactive cones. Moreover, the
gradient of cone distribution is disturbed, with S-cones becoming
widespread across the retina. The results indicate that cone
photoreceptors throughout the retina have the potential to follow a
default S-cone pathway and reveal an essential role for Trβ2 in the
commitment to an M-cone identity. Our findings raise the possibility
that Thrb mutations may be associated with human cone disorders8.
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