title: Temporal profiling of photoreceptor lineage gene expression during murine retinal development.
abstract: Rod and cone photoreceptors are photosensitive cells in the retina that convert light to electrical signals that are transmitted to visual processing centres in the brain. During development, cones and rods are generated from a common pool of multipotent retinal progenitor cells (RPCs) that also give rise to other retinal cell types. Cones and rods differentiate in two distinct waves, peaking in mid-embryogenesis and the early postnatal period, respectively. As RPCs transition from making cones to generating rods, there are changes in the expression profiles of genes involved in photoreceptor cell fate specification and differentiation. To better understand the temporal transition from cone to rod genesis, we assessed the timing of onset and offset of expression of a panel of 11 transcription factors and 7 non-transcription factors known to function in photoreceptor development, examining their expression between embryonic day (E) 12.5 and postnatal day (P) 60. Transcription factor expression in the photoreceptor layer was observed as early as E12.5, beginning with Crx, Otx2, Rorb, Neurod1 and Prdm1 expression, followed at E15.5 with the expression of Thrb, Neurog1, Sall3 and Rxrg expression, and at P0 by Nrl and Nr2e3 expression. Of the non-transcription factors, peanut agglutinin lectin staining and cone arrestin protein were observed as early as E15.5 in the developing outer nuclear layer, while transcripts for the cone opsins Opn1mw and Opn1sw and Recoverin protein were detected in photoreceptors by P0. In contrast, Opn1mw and Opn1sw protein were not observed in cones until P7, when rod-specific Gnat1 transcripts and rhodopsin protein were also detected. We have thus identified four transitory stages during murine retina photoreceptor differentiation marked by the period of onset of expression of new photoreceptor lineage genes. By characterizing these stages, we have clarified the dynamic nature of gene expression during the period when photoreceptor identities are progressively acquired during development.
authors.affiliation: Sunnybrook Research Institute, Biological Sciences Platform, Room S1-16, 2075 Bayview Ave, Toronto, ON, Canada; Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Tooka
authors.initials: T
authors.lastname: Aavani
authors.affiliation: Sunnybrook Research Institute, Biological Sciences Platform, Room S1-16, 2075 Bayview Ave, Toronto, ON, Canada; Department of Biochemistry and Molecular Biology, Cumming School of Medicine, Alberta Children's Hospital Research Institute and Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, T2N 4N1, Canada.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Tachibana
authors.affiliation: Donald K. Johnson Eye Institute, Krembil Research Institute, University Health Network and Department of Ophthalmology and Vision Sciences and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Valerie
authors.initials: V
authors.lastname: Wallace
authors.affiliation: Department of Comparative Biology and Experimental Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Biernaskie
authors.affiliation: Sunnybrook Research Institute, Biological Sciences Platform, Room S1-16, 2075 Bayview Ave, Toronto, ON, Canada; Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada; Department of Biochemistry and Molecular Biology, Cumming School of Medicine, Alberta Children's Hospital Research Institute and Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, T2N 4N1, Canada. Electronic address: cschuurm@sri.utoronto.ca.
authors.forename: Carol
authors.initials: C
authors.lastname: Schuurmans
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D008297:Male; D051379:Mice; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism*; D012160:Retina / Q000166:cytology / Q000196:embryology / Q000254:growth & development* / Q000378:metabolism; D059467:Transcriptome
chemical_list: D005136:Eye Proteins
keywords: Mouse; Retinal progenitor cells; Rod and cone photoreceptors; Temporal sequence; Transcription factors