Distinct neural stem cells proliferate in response to EGF and FGF in the developing mouse telencephalon

Distinct neural stem cells proliferate in response to EGF and FGF in the developing mouse telencephalon
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DOI:
10.1006/dbio.1998.9192
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发表时间:
1999-04-01
影响因子:
2.7
通讯作者:
van der Kooy, D
van der Kooy, D
中科院分区:
生物学3区
文献类型:
--
作者:
Tropepe, V;Sibilia, M;van der Kooy, D

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多能自我更新的神经干细胞位于胚胎小鼠端脑生发区。使用神经干细胞增殖的体外神经球测定,我们证明,FGF-反应性神经干细胞早在E8.5前神经板,但EGF-反应性神经干细胞出现在以后的发展中,在时间和空间上的具体方式。通过分别阻断EGF和FGF 2信号传导,我们还表明,单独的EGF和单独的FGF 2可以独立地引起神经干细胞增殖,并且在相对高的细胞密度下,单独的细胞非自主效应可以显著增强有丝分裂原诱导的增殖。在较低的细胞密度下,神经干细胞增殖在EGF和FGF 2组合的存在下是相加的,揭示了两种不同的干细胞群。然而,无论生长因子条件如何,FGF反应性神经干细胞和EGF反应性神经干细胞都保留其自我更新和多谱系潜能。这些结果支持了一个模型,其中单独的,谱系相关的EGF和FGF反应性神经干细胞存在于胚胎端脑生发区,(C)1999年学术出版社。
Multipotent, self-renewing neural stem cells reside in the embryonic mouse telencephalic germinal zone. Using an in vitro neurosphere assay for neural stem cell proliferation, we demonstrate that FGF-responsive neural stem cells are present as early as E8.5 in the anterior neural plate, but EGF-responsive neural stem cells emerge later in development in a temporally and spatially specific manner. By separately blocking EGF and FGF2 signaling, we also show that EGF alone and FGF2 alone can independently elicit neural stem cell proliferation and at relatively high cell densities separate cell nonautonomous effects can substantially enhance the mitogen-induced proliferation. At lower cell densities, neural stem cell proliferation is additive in the presence of EGF and FGF2 combined, revealing two different stem cell populations. However both FGF-responsive and EGF-responsive neural stem cells retain their self-renewal and multilineage potential, regardless of growth factor conditions. These results support a model in which separate, lineage-related EGF- and FGF-responsive neural stem cells are present in the embryonic telencephalic germinal zone, (C) 1999 Academic Press.