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. 2013 Apr 10;33(15):6524–6539. doi: 10.1523/JNEUROSCI.3838-12.2013

Figure 15.

Figure 15.

Model of TNFα signaling in the initiation and amplification of Müller glia proliferation during retinal regeneration. The light-damaged zebrafish retina possesses three classes of Müller glia: PPMg, SPMg, and Quiescent Müller glia (QMg). Apoptotic retinal neurons upregulate TNFα expression, which activates Ascl1a expression in the PPMg. Ascl1a drives the PPMg to re-enter the cell cycle (express PCNA) and induces Stat3 expression. Stat3 activates TNFα expression in the PPMg, which in turn, activates the expression of Ascl1a in the SPMg. The Ascl1a in the SPMg stimulates their proliferation and induces Stat3 expression. Thus, the PPMg proliferate in a TNFα-dependent and Stat3-independent manner, while re-entry of the SPMg into the cell cycle requires Stat3- and Ascl1a-dependent TNFα expression in the PPMg. The QMg express Stat3, but do not express Ascl1a and do not proliferate. It remains unknown what activates Stat3 expression in the QMg.