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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.