Abstract
Regeneration responses in animals are widespread across phyla. To identify molecular players that confer regenerative capacities to non-regenerative species is of key relevance for basic research and translational approaches. Here, we report a differential response in retinal regeneration between medaka (Oryzias latipes) and zebrafish (Danio rerio). In contrast to zebrafish, medaka Müller glia (olMG) cells behave like progenitors and exhibit a restricted capacity to regenerate the retina. After injury, olMG cells proliferate but fail to self-renew and ultimately only restore photoreceptors. In our injury paradigm, we observed that in contrast to zebrafish, proliferating olMG cells do not maintain sox2 expression. Sustained sox2 expression in olMG cells confers regenerative responses similar to those of zebrafish MG (drMG) cells. We show that a single, cell-autonomous factor reprograms olMG cells and establishes a regeneration-like mode. Our results position medaka as an attractive model to delineate key regeneration factors with translational potential.
Highlights
The ability to regenerate individual cells, lost organs or even the structure of the entire body is widespread in the animal kingdom
In contrast to zebrafish and goldfish, where Muller glia (MG) cells are described as the source of rod PRCs that gradually accumulate during the early larval period (Bernardos et al, 2007; Nelson et al, 2008), it has been shown previously that olMG cells are quiescent at a comparable developmental stage in the hatchling (8 dpf) retina (Lust et al, 2016)
We have characterized a differential regenerative response between two teleost fish and used it as a framework to address the molecular determinants of regeneration during evolution
Summary
The ability to regenerate individual cells, lost organs or even the structure of the entire body is widespread in the animal kingdom. Teleost fishes are widely used models to study development, growth and regeneration of the visual system (Centanin et al, 2011; Raymond et al, 1988, 2006; Rembold et al, 2006) The retina of these fish undergoes lifelong neurogenesis, and the range of retinal cell types is generated from two sources. Muller glial cells in medaka divide after injury, they give rise to only a single type of retinal cell. This means that these fish cannot regenerate an entire retina. Consistent with this, restoring Sox levels in medaka Muller glial cells enabled them to turn into several different types of retinal cell. We show that inducing targeted expression of sox in olMG cells is sufficient to shift olMG cells into a regenerative mode reminiscent of zebrafish, where they self-renew and regenerate multiple retinal cell types
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