title: NeuroD1 regulates expression of thyroid hormone receptor 2 and cone opsins in the developing mouse retina.
abstract: The correct patterning of opsin expression in cone photoreceptors is critical for normal color vision. Thyroid hormone, and one of its receptors [thyroid hormone receptor beta2 (TRbeta2)], is an important regulator of opsin expression during cone photoreceptor development. Mice have two genes, encoding medium-wavelength (M) and short-wavelength (S) cone opsins. Targeted deletion of TRbeta2 leads to a uniform expression of S-opsin in all cone photoreceptors and a loss of M-opsin. The control of expression of TRbeta2 is therefore central to cone differentiation, yet there is little known about its regulation in the retina. We now report that the proneural bHLH (basic helix-loop-helix) transcription factor, NeuroD1, is necessary for sustained expression of TRbeta2 in immature cone photoreceptors. Mice deficient in NeuroD1 develop an opsin phenotype virtually identical with that of TRbeta2-deficient mice: all cones express S-opsin, and none expresses M-opsin. The introduction of NeuroD1 into embryonic retinal explants from NeuroD1-/- mice restores TRbeta2 expression. NeuroD1 binds an E-box in the intron control region of the TRbeta2 gene that mediates cone-specific expression, suggesting that NeuroD1 is a critical contributory factor to the expression of TRbeta2 in cones. These results thus connect the proneural pathway with opsin selection to ensure correct cone patterning during retinal development.
authors.affiliation: Clinical Endocrinology Branch, National Institute of Diabetes and Digestive and Kidney Diseases-National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.forename: Paige
authors.initials: P
authors.lastname: Etter
authors.forename: Susan
authors.initials: S
authors.lastname: Hayes
authors.forename: Iwan
authors.initials: I
authors.lastname: Jones
authors.forename: Branden
authors.initials: B
authors.lastname: Nelson
authors.forename: Byron
authors.initials: B
authors.lastname: Hartman
authors.forename: Douglas
authors.initials: D
authors.lastname: Forrest
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Reh
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000172:deficiency / Q000502:physiology*; D001973:Bromodeoxyuridine / Q000378:metabolism; D047369:Chromatin Immunoprecipitation / Q000379:methods; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D018345:Mice, Knockout; D012160:Retina / Q000196:embryology* / Q000378:metabolism*; D017299:Rod Opsins / Q000235:genetics / Q000378:metabolism*; D037042:Thyroid Hormone Receptors beta / Q000235:genetics / Q000378:metabolism*; D014162:Transfection / Q000379:methods; D014404:Tubulin / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D001973:Bromodeoxyuridine; D049452:Green Fluorescent Proteins; D017299:Rod Opsins; D037042:Thyroid Hormone Receptors beta; D014404:Tubulin; C501008:Neurod1 protein, mouse; C462941:beta3 tubulin, mouse