The expression of tenascin-C in neural stem/progenitor cells is stimulated by the growth factors EGF and FGF-2, but not by TGFβ1

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.

Hindbrain boundaries as niches of neural progenitor and stem cells regulated by the extracellular matrix proteoglycan chondroitin sulphate

“…The milieu surrounding NPSCs in various CNS domains is enriched with different ECM proteins that dictate their proliferation, differentiation and fate ( Kazanis and ffrench-Constant, 2011 ; Preston and Sherman, 2011 ; Walma and Yamada, 2020 ). For example, the secreted glycoprotein tenascin C (TNC) and the ECM receptor integrin b (ITGB) modulate such processes in telencephalic or spinal cord NPSCs, as their loss of function decreased the number of NPSCs ( Faissner et al, 2017 ; Garcion et al, 2001 ; Karus et al, 2011 ; Temple, 2001 ; Theocharidis et al, 2021 ). Our transcriptomic analysis found that TNC , ITGB2 and ITGB5 , were upregulated in HB cells, suggesting similar role in promoting the development of the HB NPSCs.…”

Hindbrain boundaries as niches of neural progenitor/stem cells regulated by the extracellular matrix proteoglycan chondroitin sulphate

“…The milieu surrounding NPSCs in various CNS domains is enriched with different ECM proteins that dictate their proliferation, differentiation and fate (Kazanis and ffrench-Constant, 2011;Preston and Sherman, 2011;Walma and Yamada, 2020). For instance, the secreted glycoprotein Tenascin-C (TNC) and the ECM receptor integrin b (ITGB) modulate such processes in telencephalic or spinal-cord NPSCs, as their loss-of-function decreased the number of NPSCs (Faissner et al, 2017;Garcion et al, 2001;Karus et al, 2011;Temple, 2001;Theocharidis et al, 2021). Our transcriptomic analysis found that TNC and ITGB2/ITGB5, were upregulated in HB cells, suggesting similar role in promoting the development of the HB-NPSCs.…”