title: Otx2 and Onecut1 promote the fates of cone photoreceptors and horizontal cells and repress rod photoreceptors.
abstract: Cone photoreceptors carry out phototransduction in daylight conditions and provide the critical first step in color vision. Despite their importance, little is known about the developmental mechanisms involved in their generation, particularly how they are determined relative to rod photoreceptors, the cells that initiate vision in dim light. Here, we report the identification of a cis-regulatory module (CRM) for the thyroid hormone receptor beta (Thrb) gene, an early cone marker. We found that ThrbCRM1 is active in progenitor cells biased to the production of cones and an interneuronal cell type, the horizontal cell (HC). Molecular analysis of ThrbCRM1 revealed that it is combinatorially regulated by the Otx2 and Onecut1 transcription factors. Onecut1 is sufficient to induce cells with the earliest markers of cones and HCs. Conversely, interference with Onecut1 transcriptional activity leads to precocious rod development, suggesting that Onecut1 is critically important in defining cone versus rod fates.
authors.affiliation: Departments of Genetics and Ophthalmology, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Mark M
authors.initials: MM
authors.lastname: Emerson
authors.forename: Natalia
authors.initials: N
authors.lastname: Surzenko
authors.forename: Jillian J
authors.initials: JJ
authors.lastname: Goetz
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Trimarchi
authors.forename: Constance L
authors.initials: CL
authors.lastname: Cepko
mesh_terms: D000818:Animals; D019070:Cell Lineage; D002642:Chick Embryo; D002645:Chickens / Q000378:metabolism; D018274:Electroporation / Q000379:methods; D018507:Gene Expression Regulation, Developmental; D051559:Hepatocyte Nuclear Factor 6 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D051857:Otx Transcription Factors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050436:Regulatory Elements, Transcriptional; D012160:Retina / Q000166:cytology* / Q000378:metabolism; D017949:Retinal Cone Photoreceptor Cells / Q000166:cytology* / Q000378:metabolism; D017948:Retinal Rod Photoreceptor Cells / Q000166:cytology* / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism; D037042:Thyroid Hormone Receptors beta / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D051559:Hepatocyte Nuclear Factor 6; C496606:Onecut1 protein, mouse; D051857:Otx Transcription Factors; D012333:RNA, Messenger; D037042:Thyroid Hormone Receptors beta