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Figure 1
Schematic of the time course of the regenerating zebrafish retina.
Simplified diagram of a healthy retina (a). Exposure of zebrafish to constant intense light induces photoreceptor cell death (b). The dying photoreceptors are engulfed by microglia (pink, a–e, k–n) or Müller glia (green, b, c, k, l). At subsequent time points, a subset of Müller glia re-enters the cell cycle, expressing the proliferating cell nuclear antigen, PCNA (c). Proliferating Müller glia nuclei undergo interkinetic nuclear migration (INM) to the outer nuclear layer (ONL) to divide, producing a neuronal progenitor cell (NPC) and a Müller glia (d). Both nuclei return to the inner nuclear layer (INL) where the Müller glia exits the cell cycle (checkered nucleus), while the NPC continues to proliferate (e). NPCs also undergo INM (f, black and red arrows represent apical and basal migration, respectively), producing clusters of NPCs that increase expression of commitment factors that drive NPCs towards the photoreceptor lineage in the light-damaged retina (g). Committed NPCs migrate to the ONL (h), differentiating into the lost neurons to repair the damaged retina (i, checkered nuclei). In addition, a few inner retinal neurons are also produced during the regeneration time course (i, checkered nuclei in INL and ganglion cell layer (GCL)). A subregion of the ONL was magnified to display events in the ONL in detail (j–q). AC: Amacrine cell; MG: Müller glia.