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Type of publication: Journal Article
Type of document: Full Paper

Year: 2007

Authors: Applebury, ML; Farhangfar, F; Glösmann, M; Hashimoto, K; Kage, K; Robbins, JT; Shibusawa, N; Wondisford, FE; Zhang, H

Title: Transient expression of thyroid hormone nuclear receptor TRbeta2 sets S opsin patterning during cone photoreceptor genesis.

Source: Dev Dyn. 2007; 236(5):1203-1212

Authors Vetmeduni Vienna:

Glösmann Martin

Cone photoreceptors in the murine retina are patterned by dorsal repression and ventral activation of S opsin. TR beta 2, the nuclear thyroid hormone receptor beta isoform 2, regulates dorsal repression. To determine the molecular mechanism by which TR beta 2 acts, we compared the spatiotemporal expression of TR beta 2 and S opsin from embryonic day (E) 13 through adulthood in C57BL/6 retinae. TR beta 2 and S opsin are expressed in cone photoreceptors only. Both are transcribed by E13, and their levels increase with cone genesis. TR beta 2 is expressed uniformly, but transiently, across the retina. mRNA levels are maximal by E17 at completion of cone genesis and again minimal before P5. S opsin is also transcribed by E13, but only in ventral cones. Repression in dorsal cones is established by E17, consistent with the occurrence of patterning during cone cell genesis. The uniform expression of TR beta 2 suggests that repression of S opsin requires other dorsal-specific factors in addition to TR beta 2. The mechanism by which TR beta 2 functions was probed in transgenic animals with TR beta 2 ablated, TR beta 2 that is DNA binding defective, and TR beta 2 that is ligand binding defective. These studies show that TR beta 2 is necessary for dorsal repression, but not ventral activation of S opsin. TR beta 2 must bind DNA and the ligand T3 (thyroid hormone) to repress S opsin. Once repression is established, T3 no longer regulates dorsal S opsin repression in adult animals. The transient, embryonic action of TR beta 2 is consistent with a role (direct and/or indirect) in chromatin remodeling that leads to permanent gene silencing in terminally differentiated, dorsal cone photoreceptors.

Keywords Pubmed: Animals
Body Patterning
Gene Expression Regulation, Developmental
Gene Silencing
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
RNA, Messenger/genetics
RNA, Messenger/metabolism
Retinal Cone Photoreceptor Cells/embryology*
Retinal Cone Photoreceptor Cells/growth & development
Retinal Cone Photoreceptor Cells/metabolism*
Rod Opsins/genetics
Rod Opsins/metabolism*
Thyroid Hormone Receptors beta/deficiency
Thyroid Hormone Receptors beta/genetics
Thyroid Hormone Receptors beta/metabolism*

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