title: SMAD7 deficiency stimulates Müller progenitor cell proliferation during the development of the mammalian retina.
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.
authors.affiliation: Institute of Human Anatomy and Embryology, University of Regensburg, Regensburg, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Kugler
authors.affiliation: Institute of Human Anatomy and Embryology, University of Regensburg, Regensburg, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Schlecht
authors.affiliation: Institute of Human Anatomy and Embryology, University of Regensburg, Regensburg, Germany.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Fuchshofer
authors.affiliation: Institute of Human Anatomy and Embryology, University of Regensburg, Regensburg, Germany.
authors.forename: Sabrina I
authors.initials: SI
authors.lastname: Schmitt
authors.affiliation: Department of Neurology, St. Josef-Hospital, Bochum, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Kleiter
authors.affiliation: Institute of Molecular Regenerative Medicine, Spinal Cord Injury and Tissue Regeneration Center Salzburg, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Ludwig
authors.initials: L
authors.lastname: Aigner
authors.affiliation: Institute of Human Anatomy and Embryology, University of Regensburg, Regensburg, Germany.
authors.forename: Ernst R
authors.initials: ER
authors.lastname: Tamm
authors.affiliation: Institute of Human Anatomy and Embryology, University of Regensburg, Regensburg, Germany. barbara.braunger@vkl.uni-regensburg.de.
authors.forename: Barbara M
authors.initials: BM
authors.lastname: Braunger
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D051379:Mice; D018345:Mice, Knockout; D012160:Retina / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D051906:Smad7 Protein / Q000172:deficiency*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D051906:Smad7 Protein; C497807:Smad7 protein, mouse; D016212:Transforming Growth Factor beta
keywords: Müller cells; Progenitor cells; Retina; SMAD7; TGF-β signaling