Morrow T, Song M R, Ghosh A
Department of Neuroscience, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore MD 21205, USA.
Development. 2001 Sep;128(18):3585-94. doi: 10.1242/dev.128.18.3585.
Cortical progenitor cells give rise to neurons during embryonic development and to glia after birth. While lineage studies indicate that multipotent progenitor cells are capable of generating both neurons and glia, the role of extracellular signals in regulating the sequential differentiation of these cells is poorly understood. To investigate how factors in the developing cortex might influence cell fate, we developed a cortical slice overlay assay in which cortical progenitor cells are cultured over cortical slices from different developmental stages. We find that embryonic cortical progenitors cultured over embryonic cortical slices differentiate into neurons and those cultured over postnatal cortical slices differentiate into glia, suggesting that the fate of embryonic progenitors can be influenced by developmentally regulated signals. In contrast, postnatal progenitor cells differentiate into glial cells when cultured over either embryonic or postnatal cortical slices. Clonal analysis indicates that the postnatal cortex produces a diffusible factor that induces progenitor cells to adopt glial fates at the expense of neuronal fates. The effects of the postnatal cortical signals on glial cell differentiation are mimicked by FGF2 and CNTF, which induce glial fate specification and terminal glial differentiation respectively. These observations indicate that cell fate specification and terminal differentiation can be independently regulated and suggest that the sequential generation of neurons and glia in the cortex is regulated by a developmental increase in gliogenic signals.
在胚胎发育过程中，皮质祖细胞产生神经元，出生后产生胶质细胞。虽然谱系研究表明多能祖细胞能够产生神经元和胶质细胞，但细胞外信号在调节这些细胞顺序分化中的作用却知之甚少。为了研究发育中的皮质中的因子如何影响细胞命运，我们开发了一种皮质切片覆盖试验，其中将皮质祖细胞培养在来自不同发育阶段的皮质切片上。我们发现，培养在胚胎皮质切片上的胚胎皮质祖细胞分化为神经元，而培养在出生后皮质切片上的则分化为胶质细胞，这表明胚胎祖细胞的命运可受发育调控信号的影响。相比之下，出生后的祖细胞在培养于胚胎或出生后皮质切片上时都会分化为胶质细胞。克隆分析表明，出生后的皮质产生一种可扩散因子，该因子诱导祖细胞选择胶质细胞命运而牺牲神经元命运。出生后皮质信号对胶质细胞分化的影响可被FGF2和CNTF模拟，它们分别诱导胶质细胞命运特化和终末胶质细胞分化。这些观察结果表明，细胞命运特化和终末分化可被独立调节，并提示皮质中神经元和胶质细胞的顺序产生受成胶质信号的发育性增加所调控。
