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SMAD7 deficiency stimulates Müller progenitor cell proliferation during the development of the mammalian retina
Martina Kugler1, Anja Schlecht1, Rudolf Fuchshofer1
1Institute of Human Anatomy and Embryology, University of Regensburg, Regensburg, Germany.
Abstract:
The transforming growth factor-β (TGF-β) pathway contributes to maintain the quiescence of adult neural stem and progenitor cells in the brain. In the retina, Müller cells are discussed to represent a glial cell population with progenitor-like characteristics. Here, we aimed to investigate if elevated TGF-β signaling modulates the proliferation of Müller cells during retinal development. We generated mutant mice with a systemic, heterozygous up-regulation of TGF-β signaling by deleting its inhibitor SMAD7. We investigated apoptosis, proliferation, and differentiation of Müller cells in the developing retina. We show that a heterozygous deletion of SMAD7 results in an increased proliferation of Müller cell progenitors in the central retina at postnatal day 4, the time window when Müller cells differentiate in the mouse retina. This in turn results in a thickened retina and inner nuclear layer and a higher number of differentiated Müller cells in the more developed retina. Müller cells in mutant mice contain higher amounts of nestin than those of control animals which indicates that the increase in TGF-β signaling activity during retinal development contribute to maintain some progenitor-like characteristics in Müller cells even after their differentiation period. We conclude that TGF-β signaling influences Müller cell proliferation and differentiation during retinal development.
Insights
Transforming growth factor-β (TGF-β) signaling promotes Müller cell proliferation during retinal development. This leads to increased Müller cell numbers and sustained progenitor characteristics, impacting retinal structure.
Area of Science:
- Neuroscience
- Developmental Biology
- Ophthalmology
Background:
- The transforming growth factor-β (TGF-β) pathway is crucial for maintaining neural stem and progenitor cell quiescence in the brain.
- Müller cells in the retina exhibit characteristics of glial cells with progenitor-like potential.
Purpose of the Study:
- To investigate the effect of elevated TGF-β signaling on Müller cell proliferation during retinal development.
- To determine if modulating TGF-β signaling impacts Müller cell differentiation and retinal structure.
Main Methods:
- Generation of mutant mice with heterozygous upregulation of TGF-β signaling via SMAD7 deletion.
- Analysis of Müller cell apoptosis, proliferation, and differentiation in the developing retina.
- Assessment of retinal structure and Müller cell marker expression (nestin).
Main Results:
- Heterozygous SMAD7 deletion led to increased proliferation of Müller cell progenitors in the central retina at postnatal day 4.
- Mutant mice exhibited a thickened retina and inner nuclear layer with a higher number of differentiated Müller cells.
- Müller cells in mutant mice showed increased nestin expression, indicating retained progenitor-like characteristics.
Conclusions:
- TGF-β signaling positively influences Müller cell proliferation and differentiation during retinal development.
- Elevated TGF-β signaling can maintain progenitor-like features in differentiated Müller cells.
- Modulation of TGF-β pathway impacts retinal development and cellular composition.
