PuSH - Publication Server of Helmholtz Zentrum München: The extracellular matrix molecule tenascin-C modulates cell cycle progression and motility of adult neural stem/progenitor cells from the subependymal zone.

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Schaberg, E.* ; Götz, M. ; Faissner, A.*

The extracellular matrix molecule tenascin-C modulates cell cycle progression and motility of adult neural stem/progenitor cells from the subependymal zone.

Cell. Mol. Life Sci. 79:244 (2022)

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Adult neurogenesis has been described in two canonical regions of the adult central nervous system (CNS) of rodents, the subgranular zone (SGZ) of the hippocampus and the subependymal zone (SEZ) of the lateral ventricles. The stem cell niche of the SEZ provides a privileged environment composed of a specialized extracellular matrix (ECM) that comprises the glycoproteins tenascin-C (Tnc) and laminin-1 (LN1). In the present study, we investigated the function of these ECM glycoproteins in the adult stem cell niche. Adult neural stem/progenitor cells (aNSPCs) of the SEZ were prepared from wild type (Tnc^+/+) and Tnc knockout (Tnc^-/-) mice and analyzed using molecular and cell biological approaches. A delayed maturation of aNSPCs in Tnc^-/- tissue was reflected by a reduced capacity to form neurospheres in response to epidermal growth factor (EGF). To examine a potential influence of the ECM on cell proliferation, aNSPCs of both genotypes were studied by cell tracking using digital video microscopy. aNSPCs were cultivated on three different substrates, namely, poly-D-lysine (PDL) and PDL replenished with either LN1 or Tnc for up to 6 days in vitro. On each of the three substrates aNSPCs displayed lineage trees that could be investigated with regard to cell cycle length. The latter appeared reduced in Tnc^-/- aNSPCs on PDL and LN1 substrates, less so on Tnc that seemed to compensate the absence of the ECM compound to some extent. Close inspection of the lineage trees revealed a subpopulation of late dividing aNSPCs_late that engaged into cycling after a notable delay. aNSPCs_late exhibited a clearly different morphology, with a larger cell body and conspicuous processes. aNSPCs_late reiterated the reduction in cell cycle length on all substrates tested, which was not rescued on Tnc substrates. When the migratory activity of aNSPC-derived progeny was determined, Tnc^-/- neuroblasts displayed significantly longer migration tracks. This was traced to an increased rate of migration episodes compared to the wild-type cells that rested for longer time periods. We conclude that Tnc intervenes in the proliferation of aNSPCs and modulates the motility of neuroblasts in the niche of the SEZ.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Adult Neurogenesis ; Epidermal Growth Factor Receptor (egfr) ; Laminin-1 ; Lineage Tracking ; Neural Lineage ; Stem Cell Niche ; Tenascin Gene Family ; Time-lapse Video Microscopy

ISSN (print) / ISBN 1420-682X

e-ISSN 1420-9071

Journal Cellular and Molecular Life Sciences - CMLS

Quellenangaben Volume: 79, Issue: 5, Article Number: 244

Publisher Birkhäuser

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Stem Cell Research (ISF)

Grants Deutsche Forschungsgemeinschaft