Abstract
Neural stem/progenitor cells (NSPCs) rely on internal and external cues determining their lineage decisions during brain development. The progenitor cells of the embryonic mammalian forebrain reside in the ventricular and subventricular zones of the lateral ventricles, where they proliferate, generate neurons and glial cells, and respond to external cues like growth factors. The extracellular matrix (ECM) surrounds NSPCs and influences the cell fate by providing mechanical scaffold, trophic support, and instructive signals. The ECM molecule tenascin-C (Tnc) is expressed in the proliferative zones of the developing forebrain and involved in the proliferation and maturation of NSPCs. Here, we analyzed the regulation of the Tnc gene expression by NSPCs cultivated under the influence of different growth factors. We observed that the epidermal growth factor (EGF) and the fibroblast growth factor (FGF)-2 strongly increased the expression of Tnc, whereas the transforming growth factor (TGF)β 1 had no effect on Tnc gene expression, in contrast to previous findings in cell cultures of neural and non-neural origin. The stimulation of the Tnc gene expression induced by EGF or FGF-2 was reversible and seen in constantly treated as well as short term stimulated NSPC cultures. The activation depended on the presence of the respective receptors, which was slightly different in cortical and striatal NSPC cultures. Our results confirm the influence of extracellular stimuli regulating the expression of factors that form a niche for NSPCs during embryonic forebrain development.
Highlights
In the developing mammalian forebrain, neural stem/progenitor cells (NSPCs) generate the cell types of the brain in a highly ordered process, which includes the proliferation and differentiation of these cells as reviewed in several publications (e.g., Dimou and Götz 2014; Heide et al 2017; Taverna et al 2014)
Two subpopulations of progenitor cells can be distinguished in the proliferative zones of the mammalian forebrain that are characterized by their ability to respond to the epidermal growth factor (EGF) or fibroblast growth factor 2 (FGF-2)
Epidermal growth factor (EGF) and fibroblast growth factor (FGF-2) stimulate the proliferation of neural progenitors in vitro, which leads to the formation of freely floating cell aggregates, the so-called neurospheres (Ciccolini and Svendsen 1998; Reynolds et al 1992)
Summary
In the developing mammalian forebrain, neural stem/progenitor cells (NSPCs) generate the cell types of the brain in a highly ordered process, which includes the proliferation and differentiation of these cells as reviewed in several publications (e.g., Dimou and Götz 2014; Heide et al 2017; Taverna et al 2014). Two subpopulations of progenitor cells can be distinguished in the proliferative zones of the mammalian forebrain that are characterized by their ability to respond to the epidermal growth factor (EGF) or fibroblast growth factor 2 (FGF-2) (Ciccolini and Svendsen 1998; Martens et al.2000; Temple 2001; Tropepe et al 1999) These populations exhibit self-renewal and differentiation capacity, which defines them as stem cells. The responsiveness of the NSPCs to the growth factors depends on the expression of the corresponding EGF receptor (EGFR) and FGF receptor (FGFR), which are regulated in the respective manner (Burrows et al 1997; Zhu et al 1999) These receptor tyrosine kinases activate intracellular signaling cascades, including the mitogen-activated protein kinase (MAPK) pathway, which influences the proliferation
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