Park J K, Williams B P, Alberta J A, Stiles C D
Division of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
J Neurosci. 1999 Dec 1;19(23):10383-9. doi: 10.1523/JNEUROSCI.19-23-10383.1999.
Neurons and glia of the cerebral cortex are thought to arise from a common, multipotent progenitor cell that is instructed toward alternate fates by extracellular cues. How do these cells behave when confronted with conflicting cues? We show here that nestin-positive neuroepithelial (NE) cells from embryonic day 14 rat cortex coexpress surface receptor proteins for ciliary neurotrophic factor (CNTF) and platelet-derived growth factor (PDGF). Both sets of these receptor proteins are functional in NE cells, as shown by ligand-dependent activation of downstream signal-generating proteins. Transient (30') exposure to CNTF instructs NE cells toward an astrocyte fate. Brief exposure to PDGF initiates neuronal differentiation. However, when challenged with conflicting cues, PDGF is dominant to CNTF. Moreover, CNTF-treated NE cells can be "redirected" by a subsequent exposure to PDGF to form neurons instead of astrocytes, whereas the converse is not true. The asymmetric relationship between CNTF and PDGF indicates that these two growth factors act on a common progenitor cell that has, at a minimum, two fates available to it rather than separate populations of precommitted neuroblasts and astroblasts. This bipotent progenitor cell processes conflicting cues for neurons and glia in a hierarchical manner.
大脑皮层的神经元和神经胶质细胞被认为起源于一种共同的多能祖细胞，这种祖细胞通过细胞外信号被引导向不同的命运。当这些细胞面对相互冲突的信号时会有怎样的表现呢？我们在此表明，来自胚胎第14天大鼠皮层的巢蛋白阳性神经上皮（NE）细胞共表达睫状神经营养因子（CNTF）和血小板衍生生长因子（PDGF）的表面受体蛋白。如下游信号生成蛋白的配体依赖性激活所示，这两组受体蛋白在NE细胞中均具有功能。短暂（30分钟）暴露于CNTF会引导NE细胞走向星形胶质细胞命运。短暂暴露于PDGF会启动神经元分化。然而，当面对相互冲突的信号时，PDGF对CNTF具有主导作用。此外，经CNTF处理的NE细胞可以通过随后暴露于PDGF而“重新定向”以形成神经元而非星形胶质细胞，而反之则不然。CNTF和PDGF之间的不对称关系表明，这两种生长因子作用于一种至少有两种命运可供选择的共同祖细胞，而非预先确定的神经母细胞和星形胶质母细胞的不同群体。这种双能祖细胞以分层方式处理神经元和神经胶质细胞的相互冲突信号。
