Anderson D J
Division of Biology, Howard Hughes Medical Institute, Pasadena, California 91125.
J Neurobiol. 1993 Feb;24(2):185-98. doi: 10.1002/neu.480240206.
Studies of postnatal chromaffin cells, sympathetic neurons and Small Intensely Fluorescent (SIF) cells have suggested that these cells develop from a common progenitor, the sympathoadrenal (SA) progenitor, whose fate is determined by the relative levels of nerve growth factor (NGF) and glucocorticoid (GC) in its environment (Unsicker et al., 1978, Proc. Natl. Acad. Sci. USA 75:3498-3502; Doupe et al., 1985a, J. Neurosci. 5:2119-2142). Recent studies have identified such a bipotential SA progenitor in the rat embryo. Surprisingly, this progenitor is initially unresponsive to NGF; neuronal differentiation is instead promoted by fibroblast growth factor (FGF). However, FGF appears to promote NGF responsiveness, suggesting that neuronal differentiation involves a relay or cascade of growth factor action. Furthermore, chromaffin cell differentiation appears to involve two sequential, GC-dependent events: the inhibition of neuronal differentiation and the induction of epinephrine synthesis. The former event is a prerequisite to the latter. Thus both the chromaffin and neuronal pathways of differentiation follow a series of dependent events, involving changes in the responsiveness of SA progenitors to environmental factors. Such changes correlate with changes in antigenic marker expression that can be observed in vivo. In addition to choosing between neuronal and endocrine fates, SA progenitors must also express an appropriate neurotransmitter phenotype. For example, sympathetic neurons can become either noradrenergic or cholinergic. This cholinergic potential is already present in uncommitted SA progenitors, as evidenced by their ability to synthesize acetylcholine. Recent studies suggest that these cells may have yet other developmental capacities, including the ability to synthesize serotonin. This capacity is consistent with the hypothesis that SA progenitors are closely related to progenitors of enteric neurons, an idea supported by recent observations using novel antigenic markers. The SA progenitor may be, therefore, a "master" neuroendocrine progenitor for the peripheral nervous system.
对产后嗜铬细胞、交感神经元和小而密集荧光（SIF）细胞的研究表明，这些细胞由一个共同的祖细胞——交感肾上腺（SA）祖细胞发育而来，其命运由其所处环境中神经生长因子（NGF）和糖皮质激素（GC）的相对水平决定（Unsicker等人，1978年，《美国国家科学院院刊》75:3498 - 3502；Doupe等人，1985年a，《神经科学杂志》5:2119 - 2142）。最近的研究在大鼠胚胎中鉴定出了这样一种双能性SA祖细胞。令人惊讶的是，这种祖细胞最初对NGF无反应；相反，成纤维细胞生长因子（FGF）促进神经元分化。然而，FGF似乎促进了对NGF的反应性，这表明神经元分化涉及生长因子作用的接力或级联反应。此外，嗜铬细胞分化似乎涉及两个连续的、GC依赖性事件：抑制神经元分化和诱导肾上腺素合成。前一个事件是后一个事件的前提条件。因此，嗜铬细胞和神经元的分化途径都遵循一系列相关事件，涉及SA祖细胞对环境因素反应性的变化。这种变化与在体内可观察到的抗原标志物表达变化相关。除了在神经元和内分泌命运之间做出选择外，SA祖细胞还必须表达适当的神经递质表型。例如，交感神经元可以变成去甲肾上腺素能或胆碱能。这种胆碱能潜能已经存在于未分化的SA祖细胞中，这一点由它们合成乙酰胆碱的能力所证明。最近的研究表明，这些细胞可能还有其他发育能力，包括合成5 - 羟色胺的能力。这种能力与SA祖细胞与肠神经元祖细胞密切相关的假设一致，这一观点得到了最近使用新型抗原标志物的观察结果的支持。因此，SA祖细胞可能是外周神经系统的“主”神经内分泌祖细胞。
