Regulating the formation of Müller glia-derived progenitor cells in the retina

We summarize recent findings in different animal models regarding the different cell-signaling pathways and gene networks that influence the reprogramming of M & uuml;ller glia into proliferating, neurogenic progenitor cells in the retina. Not surprisingly, most of the cell-signaling pathways that guide the proliferation and differentiation of embryonic retinal progenitors also influence the ability of M & uuml;ller glia to become proliferating M & uuml;ller glia-derived progenitor cells (MGPCs). Further, the neuronal differentiation of MGPC progeny is potently inhibited by networks of neurogenesis-suppressing genes in chick and mouse models but occurs freely in zebrafish. There are important differences between the model systems, particularly pro-inflammatory signals that are active in mature M & uuml;ller glia in damaged rodent and chick retinas, but less so in fish retinas. These pro-inflammatory signals are required to initiate the process of reprogramming, but if sustained suppress the potential of M & uuml;ller glia to become neurogenic MGPCs. Further, there are important differences in how activated M & uuml;ller glia up- or downregulate pro-glial transcription factors in the different model systems. We review recent findings regarding regulatory cell signaling and gene networks that influence the activation of M & uuml;ller glia and the transition of these glia into proliferating progenitor cells with neurogenic potential in fish, chick, and mouse model systems.