Influence of the extracellular matrix molecule tenascin-C on stem cell differentiation and axonal degeneration in the adult in

نویسندگان

  • Jian Chen
  • Andrey Irintchev
  • Gabriele Loers
  • Hsing-Yin Liu
  • Sally Meiners
  • Melitta Schachner
  • Ken Muneoka
  • Masahiko Watanabe
  • Nathaniel Heintz
  • Fabio Morellini
  • Mirjam Sibbe
  • Daniel Heumann
چکیده

Extracellular matrix (ECM) molecules influence the ability of the central nervous system of adult mammals to regenerate after injury. The ECM component tenascin-C (TNC) can both promote and restrict neurite outgrowth in vitro and interact with growth factors and other ECM components. To evaluate the role of TNC in vivo, we anterogradely labeled corticospinal tract axons in wild-type (TNC+/+) and TNC deficient (TNC-/-) adult mice after spinal cord compression. We found that labeled axon die back from the lesion site over longer distances in TNC-/compared to TNC+/+ mice. This adverse response in TNC-/mice was reduced to wild-type levels by application of a TNC fragment fnD that promotes neurite outgrowth in vitro. To probe the cellular environment in the lesioned mutant versus the wild-type, we analyzed the expression of cell type-specific markers as a function of time after injury. We observed a transient appearance of GFAP/RC2/nestin positive radial glia-like cells in TNC+/+ and less in TNC-/mice. Upregulation of EGF receptor expression and activation of ERK/MAP kinase, implicated in generation of radial glia-like cells from stem cells, were also more pronounced in TNC+/+ than in TNC-/mice. The expression of TNC in TNC+/+ mice and of EGF receptor, phosphorylated ERK/MAP kinase and RC2/nestin in both genotypes was enhanced rostrally more than caudally, suggesting a functional interrelation between these molecules and the appearance of radial glia-like cells proximal to the lesion site. These observations suggest a beneficial role of tenascin-C in preservation of axon integrity via recruitment of supportive glia.

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تاریخ انتشار 2006