Wnt Signaling Promotes Regeneration in the Retina of Adult Mammals

• DOI: 10.1523/jneurosci.4193-06.2007
• Publication Date: 2007-04-11T16:58:06Z
• Authors: Fumitaka Osakada; Sotaro Ooto; Tadamichi Akagi; Michiko Mandai; Akinori Akaike; Masayo Takahashi
• Keywords: Retinal regeneration; Muller glia; WNT3A

Regeneration in the mammalian CNS is severely limited. Unlike chick, current models hold that retinal neurons are never regenerated. Previously we demonstrated that, adult retina, Müller glia dedifferentiate and produce cells, including photoreceptors, after acute neurotoxic injury vivo. However, number of newly generated very Here demonstrate Wnt (wingless-type MMTV integration site family)/beta-catenin signaling promotes proliferation glia-derived progenitors neural regeneration damage or during degeneration. Wnt3a treatment increases dedifferentiated >20-fold photoreceptor-damaged retina. Supplementation with retinoic acid valproic induces differentiation these cells primarily into Crx (cone rod homeobox)-positive rhodopsin-positive photoreceptors. Notably, nuclear accumulation beta-catenin, cyclin D1 upregulation, Wnt/beta-catenin reporter activity. Activation by glycogen synthase kinase-3beta inhibitors regeneration, and, conversely, inhibition attenuates regeneration. This Wnt3a-mediated also occurs rd mice, a model These results provide evidence contributes to mammal.