Reinhard Fässler

Publications (3)22.97 Total impact

• Source

  Available from: Dies Meijer

  Article: Integrin-linked kinase is required for radial sorting of axons and Schwann cell remyelination in the peripheral nervous system.

  Jorge A Pereira, Yves Benninger, Reto Baumann, Ana Filipa Gonçalves, Murat Ozçelik, Tina Thurnherr, Nicolas Tricaud, Dies Meijer, Reinhard Fässler, Ueli Suter, João B Relvas
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  ABSTRACT: During development, Schwann cells (SCs) interpret different extracellular cues to regulate their migration, proliferation, and the remarkable morphological changes associated with the sorting, ensheathment, and myelination of axons. Although interactions between extracellular matrix proteins and integrins are critical to some of these processes, the downstream signaling pathways they control are still poorly understood. Integrin-linked kinase (ILK) is a focal adhesion protein that associates with multiple binding partners to link integrins to the actin cytoskeleton and is thought to participate in integrin and growth factor-mediated signaling. Using SC-specific gene ablation, we report essential functions for ILK in radial sorting of axon bundles and in remyelination in the peripheral nervous system. Our in vivo and in vitro experiments show that ILK negatively regulates Rho/Rho kinase signaling to promote SC process extension and to initiate radial sorting. ILK also facilitates axon remyelination, likely by promoting the activation of downstream molecules such as AKT/protein kinase B.
  The Journal of Cell Biology 05/2009; 185(1):147-61. · 10.26 Impact Factor
• Article: Regulation of neural progenitor proliferation and survival by beta1 integrins.

  Dino P Leone, João B Relvas, Lia S Campos, Silvio Hemmi, Cord Brakebusch, Reinhard Fässler, Charles Ffrench-Constant, Ueli Suter
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  ABSTRACT: Neural stem cells give rise to undifferentiated nestin-positive progenitors that undergo extensive cell division before differentiating into neuronal and glial cells. The precise control of this process is likely to be, at least in part, controlled by instructive cues originating from the extracellular environment. Some of these cues are interpreted by the integrin family of extracellular matrix receptors. Using neurosphere cell cultures as a model system, we show that beta1-integrin signalling plays a crucial role in the regulation of progenitor cell proliferation, survival and migration. Following conditional genetic ablation of the beta1-integrin allele, and consequent loss of beta1-integrin cell surface protein, mutant nestin-positive progenitor cells proliferate less and die in higher numbers than their wild-type counterparts. Mutant progenitor cell migration on different ECM substrates is also impaired. These effects can be partially compensated by the addition of exogenous growth factors. Thus, beta1-integrin signalling and growth factor signalling tightly interact to control the number and migratory capacity of nestin-positive progenitor cells.
  Journal of Cell Science 07/2005; 118(Pt 12):2589-99. · 6.11 Impact Factor
• Article: Beta1 integrins activate a MAPK signalling pathway in neural stem cells that contributes to their maintenance.

  Lia S Campos, Dino P Leone, Joao B Relvas, Cord Brakebusch, Reinhard Fässler, Ueli Suter, Charles ffrench-Constant
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  ABSTRACT: The emerging evidence that stem cells develop in specialised niches highlights the potential role of environmental factors in their regulation. Here we examine the role of beta1 integrin/extracellular matrix interactions in neural stem cells. We find high levels of beta1 integrin expression in the stem-cell containing regions of the embryonic CNS, with associated expression of the laminin alpha2 chain. Expression levels of laminin alpha2 are reduced in the postnatal CNS, but a population of cells expressing high levels of beta1 remains. Using neurospheres - aggregate cultures, derived from single stem cells, that have a three-dimensional architecture that results in the localisation of the stem cell population around the edge of the sphere - we show directly that beta1 integrins are expressed at high levels on neural stem cells and can be used for their selection. MAPK, but not PI3K, signalling is required for neural stem cell maintenance, as assessed by neurosphere formation, and inhibition or genetic ablation of beta1 integrin using cre/lox technology reduces the level of MAPK activity. We conclude that integrins are therefore an important part of the signalling mechanisms that control neural stem cell behaviour in specific areas of the CNS.
  Development 08/2004; 131(14):3433-44. · 6.60 Impact Factor