层粘连蛋白-C 在神经干细胞/祖细胞中的表达受生长因子 EGF 和 FGF-2 的刺激,但不受 TGFβ1 的影响。

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

机构信息

Department of Cell Morphology and Molecular Neurobiology, Ruhr University Bochum, Bochum, Germany.

出版信息

Cell Tissue Res. 2021 Sep;385(3):659-674. doi: 10.1007/s00441-021-03508-6. Epub 2021 Jul 26.

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.

摘要

神经干细胞/祖细胞(NSPCs)依赖于内部和外部线索来决定它们在大脑发育过程中的谱系决策。哺乳动物胚胎前脑的祖细胞位于侧脑室的室管膜和室下区,在那里它们增殖、产生神经元和神经胶质细胞,并对外界线索(如生长因子)做出反应。细胞外基质(ECM)围绕着 NSPCs,并通过提供机械支架、营养支持和指导信号来影响细胞命运。细胞外基质分子 tenascin-C(Tnc)在前脑发育的增殖区表达,并参与 NSPCs 的增殖和成熟。在这里,我们分析了 NSPC 在不同生长因子影响下培养时 Tnc 基因表达的调节。我们观察到表皮生长因子(EGF)和成纤维细胞生长因子 2(FGF-2)强烈增加了 Tnc 的表达,而转化生长因子β 1(TGFβ 1)对 Tnc 基因表达没有影响,这与先前在神经和非神经来源的细胞培养中的发现相反。EGF 或 FGF-2 诱导的 Tnc 基因表达的刺激是可逆的,并且在持续处理和短期刺激的 NSPC 培养中都可以看到。这种激活依赖于各自受体的存在,而在皮质和纹状体 NSPC 培养物中,受体的存在略有不同。我们的结果证实了细胞外刺激对调节 NSPCs 形成胚胎前脑发育龛位的因子表达的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a7a1/8526465/8afa30d92464/441_2021_3508_Fig1_HTML.jpg

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