title: Expression of Two Classes of Pax6 Transcripts in Reprogramming Retinal Pigment Epithelium Cells of the Adult Newt.
abstract: The adult newt has the remarkable ability to regenerate a functional retina from retinal pigment epithelium (RPE) cells, even when the neural retina (NR) is completely lost from the eye. In this system, RPE cells are reprogrammed into a unique state of multipotent cells, named RPESCs, in an early phase of retinal regeneration. However, the signals that trigger reprogramming remain unknown. Here, to approach this issue we focused on Pax6, a transcription factor known to be expressed in RPESCs. We first identified four classes (v1, v2, v3 and v4) of Pax6 variants in the eye of adult newt, Cynops pyrrhogaster. These variants were expressed in most tissues of the intact eye in different combinations but not in the RPE, choroid or sclera. On the basis of this information, we investigated the expression of Pax6 in RPE cells after the NR was removed from the eye by surgery (retinectomy), and found that two classes (v1 and v2) of Pax6 variants were newly expressed in RPE cells 10 days after retinectomy, both in vivo and in vitro (RLEC system). In the RLEC system, we found that Pax6 expression is mediated through a pathway separate from the MEK-ERK pathway, which is required for cell cycle re-entry of RPE cells. These results predict the existence of a pathway that may be of fundamental importance to a better understanding of the reprogramming of RPE cells in vivo.
authors: 1 Graduate School of Life and Environmental Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki 305-8572, Japan.
authors: Wataru
authors: W
authors: Inami
authors: 1 Graduate School of Life and Environmental Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki 305-8572, Japan.
authors: Md Rafiqul
authors: MR
authors: Islam
authors: 2 Faculty of Life and Environmental Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki 305-8572, Japan.
authors: Kenta
authors: K
authors: Nakamura
authors: 1 Graduate School of Life and Environmental Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki 305-8572, Japan.
authors: Taro
authors: T
authors: Yoshikawa
authors: 1 Graduate School of Life and Environmental Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki 305-8572, Japan.
authors: Hirofumi
authors: H
authors: Yasumuro
authors: 2 Faculty of Life and Environmental Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki 305-8572, Japan.
authors: Martin Miguel
authors: MM
authors: Casco-Robles
authors: 3 Graduate School of Engineering, Utsunomiya University, Yoto 7-1-2, Utsunomiya, Tochigi 321-8585, Japan.
authors: Fubito
authors: F
authors: Toyama
authors: 2 Faculty of Life and Environmental Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki 305-8572, Japan.
authors: Fumiaki
authors: F
authors: Maruo
authors: 2 Faculty of Life and Environmental Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki 305-8572, Japan.
authors: Chikafumi
authors: C
authors: Chiba
mesh_terms: D000818:Animals; D001483:Base Sequence; D002070:Butadienes / Q000494:pharmacology; D004247:DNA / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D014644:Genetic Variation; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D055213:Retinal Pigment Epithelium / Q000166:cytology* / Q000502:physiology*; D012455:Salamandridae / Q000502:physiology*
chemical_list: D002070:Butadienes; D004791:Enzyme Inhibitors; D005136:Eye Proteins; D018398:Homeodomain Proteins; D009570:Nitriles; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins; C113580:U 0126; D004247:DNA
keywords: ERK; MEK; Pax6; cell cycle; newt; reprogramming; retinal pigment epithelium; retinal regeneration