title: Rax Homeoprotein Regulates Photoreceptor Cell Maturation and Survival in Association with Crx in the Postnatal Mouse Retina.
abstract: The Rax homeobox gene plays essential roles in multiple processes of vertebrate retina development. Many vertebrate species possess Rax and Rax2 genes, and different functions have been suggested. In contrast, mice contain a single Rax gene, and its functional roles in late retinal development are still unclear. To clarify mouse Rax function in postnatal photoreceptor development and maintenance, we generated conditional knockout mice in which Rax in maturing or mature photoreceptor cells was inactivated by tamoxifen treatment (Rax iCKO mice). When Rax was inactivated in postnatal Rax iCKO mice, developing photoreceptor cells showed a significant decrease in the level of the expression of rod and cone photoreceptor genes and mature adult photoreceptors exhibited a specific decrease in cone cell numbers. In luciferase assays, we found that Rax and Crx cooperatively transactivate Rhodopsin and cone opsin promoters and that an optimum Rax expression level to transactivate photoreceptor gene expression exists. Furthermore, Rax and Crx colocalized in maturing photoreceptor cells, and their coimmunoprecipitation was observed in cultured cells. Taken together, these results suggest that Rax plays essential roles in the maturation of both cones and rods and in the survival of cones by regulating photoreceptor gene expression with Crx in the postnatal mouse retina.
authors.affiliation: Laboratory for Molecular and Developmental Biology, Institute for Protein Research, Osaka University, Suita, Osaka, Japan Japan Science and Technology Agency, Core Research for Evolutional Science and Technology, Suita, Osaka, Japan Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Shoichi
authors.initials: S
authors.lastname: Irie
authors.affiliation: Laboratory for Molecular and Developmental Biology, Institute for Protein Research, Osaka University, Suita, Osaka, Japan Japan Science and Technology Agency, Core Research for Evolutional Science and Technology, Suita, Osaka, Japan.
authors.forename: Rikako
authors.initials: R
authors.lastname: Sanuki
authors.affiliation: Laboratory for Molecular and Developmental Biology, Institute for Protein Research, Osaka University, Suita, Osaka, Japan Japan Science and Technology Agency, Core Research for Evolutional Science and Technology, Suita, Osaka, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Muranishi
authors.affiliation: Laboratory for Molecular and Developmental Biology, Institute for Protein Research, Osaka University, Suita, Osaka, Japan Japan Science and Technology Agency, Core Research for Evolutional Science and Technology, Suita, Osaka, Japan.
authors.forename: Kimiko
authors.initials: K
authors.lastname: Kato
authors.affiliation: Laboratory for Molecular and Developmental Biology, Institute for Protein Research, Osaka University, Suita, Osaka, Japan Japan Science and Technology Agency, Core Research for Evolutional Science and Technology, Suita, Osaka, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Chaya
authors.affiliation: Laboratory for Molecular and Developmental Biology, Institute for Protein Research, Osaka University, Suita, Osaka, Japan Japan Science and Technology Agency, Core Research for Evolutional Science and Technology, Suita, Osaka, Japan takahisa.furukawa@protein.osaka-u.ac.jp.
authors.forename: Takahisa
authors.initials: T
authors.lastname: Furukawa
mesh_terms: D016475:3T3 Cells; D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D055358:Cone Opsins / Q000096:biosynthesis / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism; D057809:HEK293 Cells; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009457:Neuroglia / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism*; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism*; D012243:Rhodopsin / Q000096:biosynthesis / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation / Q000235:genetics*
chemical_list: D055358:Cone Opsins; D005136:Eye Proteins; D018398:Homeodomain Proteins; C105441:Rax protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; C109288:cone rod homeobox protein; D012243:Rhodopsin