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Publication : Transcriptional control of cone photoreceptor diversity by a thyroid hormone receptor.

First Author  Aramaki M Year  2022
Journal  Proc Natl Acad Sci U S A Volume  119
Issue  49 Pages  e2209884119
PubMed ID  36454759 Mgi Jnum  J:345089
Mgi Id  MGI:7487951 Doi  10.1073/pnas.2209884119
Citation  Aramaki M, et al. (2022) Transcriptional control of cone photoreceptor diversity by a thyroid hormone receptor. Proc Natl Acad Sci U S A 119(49):e2209884119
abstractText  Cone photoreceptor diversity allows detection of wavelength information in light, the first step in color (chromatic) vision. In most mammals, cones express opsin photopigments for sensitivity to medium/long (M, "green") or short (S, "blue") wavelengths and are differentially arrayed over the retina. Cones appear early in retinal neurogenesis but little is understood of the subsequent control of diversity of these postmitotic neurons, because cone populations are sparse and, apart from opsins, poorly defined. It is also a challenge to distinguish potentially subtle differences between cell subtypes within a lineage. Therefore, we derived a Cre driver to isolate individual M and S opsin-enriched cones, which are distributed in counter-gradients over the mouse retina. Fine resolution transcriptome analyses identified expression gradients for groups of genes. The postnatal emergence of gradients indicated divergent differentiation of cone precursors during maturation. Using genetic tagging, we demonstrated a role for thyroid hormone receptor beta2 (TRbeta2) in control of gradient genes, many of which are enriched for TRbeta2 binding sites and TRbeta2-regulated open chromatin. Deletion of TRbeta2 resulted in poorly distinguished cones regardless of retinal location. We suggest that TRbeta2 controls a bipotential transcriptional state to promote cone diversity and the chromatic potential of the species.
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