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Biol Open. 2018 Jul 25;7(7). pii: bio027730. doi: 10.1242/bio.027730.

Cell tracking in vitro reveals that the extracellular matrix glycoprotein Tenascin-C modulates cell cycle length and differentiation in neural stem/progenitor cells of the developing mouse spinal cord.

Author information

1
Department for Cell Morphology and Molecular Neurobiology, Ruhr-University Bochum, 44780 Bochum, Germany.
2
Aachen Interdisciplinary Center for Clinical Research, Faculty of Medicine, Rheinisch-Westfälische Technische Hochschule Aachen, 52074 Aachen, Germany.
3
Department of Biosystems Science and Engineering, ETH Zürich, 4058 Basel, Switzerland.
4
Physiological Genomics, Biomedical Center, Ludwig-Maximilians University Munich, 82152 Planegg/Martinsried, Germany.
5
Department of Physiological Genomics, Biomedical Center, Ludwig-Maximilians University Munich, 82152 Planegg/Martinsried, Germany.
6
Munich Cluster for Systems Neurology (SyNergy), Ludwig-Maximilians University Munich, 81377 Munich, Germany.
7
Department for Cell Morphology and Molecular Neurobiology, Ruhr-University Bochum, 44780 Bochum, Germany andreas.faissner@rub.de.

Abstract

Generation of astrocytes during the development of the mammalian spinal cord is poorly understood. Previously, we have shown that the glycoprotein of the extracellular matrix (ECM) tenascin-C (Tnc) modulates the expression territories of the patterning genes Nkx6.1 and Nkx2.2 in the developing ventral spinal cord, tunes the responsiveness of neural stem/progenitor cells towards the cytokines FGF2 and EGF and thereby promotes astrocyte maturation. In order to obtain further mechanistic insight into these processes, we have compared embryonic day-15 spinal cord neural progenitor cells (NPCs) from wild-type and Tnc knockout mice using continuous single-cell live imaging and cell lineage analysis in vitroTnc knockout cells displayed a significantly reduced rate of cell division both in response to FGF2 and EGF. When individual clones of dividing cells were investigated with regard to their cell lineage trees using the tTt tracking software, it appeared that the cell cycle length in response to growth factors was reduced in the knockout. Furthermore, when Tnc knockout NPCs were induced to differentiate by the removal of FGF2 and EGF glial differentiation was enhanced. We conclude that the constituent of the stem cell niche Tnc contributes to preserve stemness of NPCs.

KEYWORDS:

Cell lineage; Extracellular matrix; Gliogenesis; Growth factor responsiveness; Stem cell niche; Tenascin-C; Time-lapse video microscopy

Conflict of interest statement

Competing interestsThe authors declare no competing or financial interests.

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