First Author | Applebury ML | Year | 2007 |
Journal | Dev Dyn | Volume | 236 |
Issue | 5 | Pages | 1203-12 |
PubMed ID | 17436273 | Mgi Jnum | J:121116 |
Mgi Id | MGI:3709254 | Doi | 10.1002/dvdy.21155 |
Citation | Applebury ML, et al. (2007) Transient expression of thyroid hormone nuclear receptor TRbeta2 sets S opsin patterning during cone photoreceptor genesis. Dev Dyn 236(5):1203-12 |
abstractText | Cone photoreceptors in the murine retina are patterned by dorsal repression and ventral activation of S opsin. TRbeta2, the nuclear thyroid hormone receptor beta isoform 2, regulates dorsal repression. To determine the molecular mechanism by which TRbeta2 acts, we compared the spatiotemporal expression of TRbeta2 and S opsin from embryonic day (E) 13 through adulthood in C57BL/6 retinae. TRbeta2 and S opsin are expressed in cone photoreceptors only. Both are transcribed by E13, and their levels increase with cone genesis. TRbeta2 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 TRbeta2 suggests that repression of S opsin requires other dorsal-specific factors in addition to TRbeta2. The mechanism by which TRbeta2 functions was probed in transgenic animals with TRbeta2 ablated, TRbeta2 that is DNA binding defective, and TRbeta2 that is ligand binding defective. These studies show that TRbeta2 is necessary for dorsal repression, but not ventral activation of S opsin. TRbeta2 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 TRbeta2 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. (c) 2007 Wiley-Liss, Inc. |