Anderson D J, Michelsohn A
Division of Biology, California Institute of Technology, Pasadena 91125.
Int J Dev Neurosci. 1989;7(5):475-87. doi: 10.1016/0736-5748(89)90007-5.
Chromaffin cells and sympathetic neurons develop from a common neural crest-derived progenitor cell. The developmental fate of this cell differs depending upon whether it migrates to the sympathetic ganglion or to the adrenal gland primordium, suggesting that local environmental signals control its differentiation. Glucocorticoid (GC) is a good candidate for an important adrenal environmental signal. These steroids are known to regulate PNMT, an adrenal-specific enzyme. However, in vivo observations suggest that the adrenal microenvironment influences the phenotype of sympatho-adrenal progenitor cells as early as E14.5, 2 days before PNMT is first expressed by developing chromaffin cells. Using cDNA probes, we find that GC receptor mRNA can be detected in the embryonic adrenal at least one full day before the initial appearance of PNMT mRNA. This observation is compatible with the idea that the apparent early influence of the adrenal microenvironment reflects the action of GC on progenitors which have migrated into this environment. In support of this, we show that similar influences can be exerted by GC on PC12 cells, which contain GC receptor mRNA but do not express or induce PNMT mRNA. Taken together, these data suggest that other factors in addition to the presence of the GC receptor may be necessary for the developmental appearance of PNMT expression.
嗜铬细胞和交感神经元由共同的神经嵴衍生祖细胞发育而来。该细胞的发育命运因其迁移至交感神经节还是肾上腺原基而有所不同,这表明局部环境信号控制着其分化。糖皮质激素(GC)是一种重要的肾上腺环境信号的有力候选者。已知这些类固醇可调节PNMT,一种肾上腺特异性酶。然而,体内观察表明,早在胚胎第14.5天,即发育中的嗜铬细胞首次表达PNMT的前两天,肾上腺微环境就会影响交感 - 肾上腺祖细胞的表型。使用cDNA探针,我们发现至少在PNMT mRNA最初出现的一整天前,就能在胚胎肾上腺中检测到GC受体mRNA。这一观察结果与肾上腺微环境的明显早期影响反映了GC对已迁移到该环境中的祖细胞的作用这一观点相符。为此,我们表明GC对PC12细胞也能产生类似影响,PC12细胞含有GC受体mRNA,但不表达或诱导PNMT mRNA。综上所述,这些数据表明,除了GC受体的存在外,其他因素可能对于PNMT表达的发育出现也是必要的。