The Circadian Clock Gene Bmal1 Controls Thyroid Hormone-Mediated Spectral Identity and Cone Photoreceptor Function

Publication date: 17 October 2017
Source:Cell Reports, Volume 21, Issue 3
Author(s): Onkar B. Sawant, Amanda M. Horton, Olivia F. Zucaro, Ricky Chan, Vera L. Bonilha, Ivy S. Samuels, Sujata Rao
Circadian clocks regulate various aspects of photoreceptor physiology, but their contribution to photoreceptor development and function is unclear. Cone photoreceptors are critical for color vision. Here, we define the molecular function of circadian activity within cone photoreceptors and reveal a role for the clock genes Bmal1 and Per2 in regulating cone spectral identity. ChIP analysis revealed that BMAL1 binds to the promoter region of the thyroid hormone (TH)-activating enzyme type 2 iodothyronine deiodinase (Dio2) and thus regulates the expression of Dio2. TH treatment resulted in a partial rescue of the phenotype caused by the loss of Bmal1, thus revealing a functional relationship between Bmal1 and Dio2 in establishing cone photoreceptor identity. Furthermore, Bmal1 and Dio2 are required to maintain cone photoreceptor functional integrity. Overall, our results suggest a mechanism by which circadian proteins can locally regulate the availability of TH and influence tissue development and function.

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Teaser

Short- and medium-wavelength opsins in cone photoreceptors are required for color vision. Sawant et al. show that core circadian clock genes are required for cone opsin expression, gradient maintenance, and cone function and that these effects are mediated by regulation of thyroid hormone signaling.


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