The transforming growth factor-beta (TGF-beta) pathway contributes to maintain the quiescence of adult neural stem and progenitor cells in the brain. In the retina, Muller cells are discussed to represent a glial cell population with progenitor-like characteristics. Here, we aimed to investigate if elevated TGF-beta signaling modulates the proliferation of Muller cells during retinal development. We generated mutant mice with a systemic, heterozygous up-regulation of TGF-beta signaling by deleting its inhibitor SMAD7. We investigated apoptosis, proliferation, and differentiation of Muller cells in the developing retina. We show that a heterozygous deletion of SMAD7 results in an increased proliferation of Muller cell progenitors in the central retina at postnatal day 4, the time window when Muller cells differentiate in the mouse retina. This in turn results in a thickened retina and inner nuclear layer and a higher number of differentiated Muller cells in the more developed retina. Muller cells in mutant mice contain higher amounts of nestin than those of control animals which indicates that the increase in TGF-beta signaling activity during retinal development contribute to maintain some progenitor-like characteristics in Muller cells even after their differentiation period. We conclude that TGF-beta signaling influences Muller cell proliferation and differentiation during retinal development.
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