Histochemistry and Cell Biology

, Volume 148, Issue 1, pp 21–32 | Cite as

SMAD7 deficiency stimulates Müller progenitor cell proliferation during the development of the mammalian retina

  • Martina Kugler
  • Anja Schlecht
  • Rudolf Fuchshofer
  • Sabrina I. Schmitt
  • Ingo Kleiter
  • Ludwig Aigner
  • Ernst R. Tamm
  • Barbara M. Braunger
Original Paper


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.


SMAD7 TGF-β signaling Müller cells Progenitor cells Retina 



The authors would like to thank Elke Stauber, Angelika Pach, Margit Schimmel, and Silvia Babl for their excellent technical assistance. This work is supported by Deutsche Forschungsgemeinschaft Grant FOR 1075 (TP9).


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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Martina Kugler
    • 1
  • Anja Schlecht
    • 1
  • Rudolf Fuchshofer
    • 1
  • Sabrina I. Schmitt
    • 1
  • Ingo Kleiter
    • 2
  • Ludwig Aigner
    • 3
  • Ernst R. Tamm
    • 1
  • Barbara M. Braunger
    • 1
  1. 1.Institute of Human Anatomy and EmbryologyUniversity of RegensburgRegensburgGermany
  2. 2.Department of NeurologySt. Josef-HospitalBochumGermany
  3. 3.Institute of Molecular Regenerative Medicine, Spinal Cord Injury and Tissue Regeneration Center SalzburgParacelsus Medical UniversitySalzburgAustria

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