title: Evidence for Notch signaling involvement in retinal regeneration of adult newt.
abstract: Involvement of Notch signaling in retinal regeneration by transdifferentiation of pigment epithelium cells was investigated using the adult newt Cynops pyrrhogaster. During retinal regeneration, cells expressing Notch-1 first appeared in the regenerating retina one to two cells thick (stage E-3) originated from the retinal pigment epithelium (RPE) cells, and increased in number as the regenerating retina increased in thickness. Notch-1 expression was decreased in the central retina in association with cell differentiation and became restricted to the peripheral retina. Administration of a Notch signaling blocker DAPT resulted in the appearance of a cluster of neurons, earlier than in normal regeneration, along the regenerating retina 1-3 cells thick (stage E-3 to I-1). Immunoblot analysis suggested that DAPT could perturb the processing of Notch-1. Similar results were obtained in the newt embryonic retinal development. These results suggest that the Notch-1 signaling system may be reset to regulate neurogenesis during retinal regeneration. However, PCR analysis revealed that the adult newt RPE cells express Hes-1, neurogenin1 and sometimes Delta-1 Hes-1, neurogenin1 and sometimes Delta-1 all of which are differently regulated in association with retinal regeneration, implying that Notch signaling might also be involved early in the process of transdifferentiation.
authors.affiliation: Life and Environmental Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki 305-8572, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Nakamura
authors.forename: Chikafumi
authors.initials: C
authors.lastname: Chiba
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D003001:Cloning, Molecular; D004625:Embryo, Nonmammalian; D005136:Eye Proteins / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology*; D010857:Pigment Epithelium of Eye / Q000378:metabolism; D051880:Receptors, Notch / Q000502:physiology*; D012160:Retina / Q000187:drug effects / Q000503:physiopathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012455:Salamandridae / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014280:Triglycerides / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D005136:Eye Proteins; D051880:Receptors, Notch; D014280:Triglycerides; D005680:gamma-Aminobutyric Acid; C057077:1,2-dilinolenoyl-3-(4-aminobutyryl)propane-1,2,3-triol