Tenascin C Regulates Proliferation and Differentiation Processes During Embryonic Retinogenesis and Modulates the De-Differentiation Capacity of Müller Glia by Influencing Growth Factor Responsiveness and the Extracellular Matrix Compartment

Dev Biol. 2012 Sep 15;369(2):163-76. doi: 10.1016/j.ydbio.2012.05.020. Epub 2012 Jun 9.

Abstract

The retina represents an ideal model system for studying developmental processes during morphogenesis. The knowledge of the precise regulation and combination of genetic pre-dispositions and environmental circumstances enables the understanding of pathologies and the subsequent development or/and improvement of therapeutic strategies. This study focused on the functional analysis of the extracellular matrix (ECM) molecule Tenascin C (Tnc) in the retinal stem/progenitor cell environment. In this perspective, a Tnc(-/-) mouse was examined for potential alterations in proliferation and differentiation programs by using immunohistochemistry, RT-PCR analysis and bioassays. It could be shown that both cycling G2-phase cells and early post-mitotic neurons were significantly increased in the retina due to Tnc-deficiency. Further investigations suggested that Tnc regulates these processes via the Wnt-signaling cascade. Therapeutic approaches in the treatment of degenerative diseases often integrate cell-replacement strategies. Retinal Müller glia cells represent the glia of the retina and are described to possess the ability to re-enter the cell cycle and generate neurons in response to injury. In this study, the de-differentiation was induced by FGF2. It was found out that Tnc influences the de-differentiation behavior of adherent Müller glia in vitro. Moreover, it was interesting to investigate the effect of the absence of Tnc on the composition of other components of the ECM. A special focus lay on the expression of a specifically sulfated carbohydrate motif on chondroitin sulfate glycosaminoglycan chains, which can be detected with the mAb 473HD. It was possible to note a significant increase of this particular chondroitin sulfate in the Tnc-deficient ECM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Compartmentation
  • Cell Cycle Checkpoints
  • Cell Dedifferentiation
  • Cell Differentiation
  • Cell Proliferation
  • Chondroitin Sulfate Proteoglycans / metabolism
  • Extracellular Matrix / physiology
  • Fibroblast Growth Factor 2 / pharmacology
  • Fibroblast Growth Factor 2 / physiology
  • G2 Phase
  • Mice
  • Mice, 129 Strain
  • Mice, Knockout
  • Neuroglia / cytology*
  • Neuroglia / physiology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptor, Fibroblast Growth Factor, Type 1 / genetics
  • Receptor, Fibroblast Growth Factor, Type 1 / metabolism
  • Receptor, Fibroblast Growth Factor, Type 2 / genetics
  • Receptor, Fibroblast Growth Factor, Type 2 / metabolism
  • Retina / cytology*
  • Retina / embryology*
  • Retina / physiology
  • Tenascin / deficiency
  • Tenascin / genetics
  • Tenascin / physiology*

Substances

  • Chondroitin Sulfate Proteoglycans
  • RNA, Messenger
  • Tenascin
  • Fibroblast Growth Factor 2
  • Fgfr1 protein, mouse
  • Fgfr2 protein, mouse
  • Receptor, Fibroblast Growth Factor, Type 1
  • Receptor, Fibroblast Growth Factor, Type 2