Poster abstracts
Poster number 86 submitted by Levi Todd
Hedgehog signaling in the formation of Muller glia-derived progenitor cells.
Levi Todd (Department of Neuroscience), Andy Fischer (Department of Neuroscience)
Abstract:
The capacity of retinal regeneration varies substantially across vertebrate species, but consistently involves Müller glia as the cellular source for progenitors. Although retinal regeneration is robust in fish, the regeneration in birds and mammals is limited. However, after retinal injury, Müller glia in the avian retina are able to undergo a program of de-differentiation, proliferation, and neurogenesis. The signaling pathways that influence the formation of Müller glia-derived progenitor cells (MGPCs) are slowly being revealed. The purpose of this study was to investigate whether Hedgehog-signaling is a key node in the signaling network that orchestrates the regenerative response of MGPCs. In damaged retinas, we found that Hedgehog-signaling is dynamically up-regulated in Müller glia/MGPCs, and inhibition of Hedgehog-signaling decreases numbers of MGPCs. By comparison, activation of Hedgehog-signaling increases the formation of MGPCS in moderately damaged retinas, but is not sufficient to induce the formation of MGPCs in the absence of injury. Fibroblast growth factor 2 (FGF2) alone induces the formation of MGPCs in undamaged retina. We found that Hedgehog-signaling is necessary for FGF2-induced MGPC formation as Hedgehog inhibition prevents progenitor cell formation. Additionally, co-application of Hedgheog agonists with FGF2 leads to an increase of MGPC formation. We conclude that Hedgehog-signaling stimulates the formation of proliferating MGPCs in acutely damaged retinas. Further, in undamaged retinas, our data indicate that FGF2/MAPK-signaling recruits Hedgehog-signaling to boost the regenerative response of MGPCs.
Keywords: retina, glia, regeneration