Premium
Transient expression of thyroid hormone nuclear receptor TRβ2 sets S opsin patterning during cone photoreceptor genesis
Author(s) -
Applebury M.L.,
Farhangfar F.,
Glösmann M.,
Hashimoto K.,
Kage K.,
Robbins J.T.,
Shibusawa N.,
Wondisford F.E.,
Zhang H.
Publication year - 2007
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.21155
Subject(s) - opsin , biology , psychological repression , retina , microbiology and biotechnology , nuclear receptor , receptor , anatomy , transcription factor , genetics , gene expression , gene , neuroscience , rhodopsin , biochemistry , retinal
Cone photoreceptors in the murine retina are patterned by dorsal repression and ventral activation of S opsin. TRβ2, the nuclear thyroid hormone receptor β isoform 2, regulates dorsal repression. To determine the molecular mechanism by which TRβ2 acts, we compared the spatiotemporal expression of TRβ2 and S opsin from embryonic day (E) 13 through adulthood in C57BL/6 retinae. TRβ2 and S opsin are expressed in cone photoreceptors only. Both are transcribed by E13, and their levels increase with cone genesis. TRβ2 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 TRβ2 suggests that repression of S opsin requires other dorsal‐specific factors in addition to TRβ2. The mechanism by which TRβ2 functions was probed in transgenic animals with TRβ2 ablated, TRβ2 that is DNA binding defective, and TRβ2 that is ligand binding defective. These studies show that TRβ2 is necessary for dorsal repression, but not ventral activation of S opsin. TRβ2 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 TRβ2 is consistent with a role (direct and/or indirect) in chromatin remodeling that leads to permanent gene silencing in terminally differentiated, dorsal cone photoreceptors. Developmental Dynamics 236:1203–1212, 2007. © 2007 Wiley‐Liss, Inc.