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首页> 外文期刊>Development >Sequential specification of neurons and glia by developmentally regulated extracellular factors.
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Sequential specification of neurons and glia by developmentally regulated extracellular factors.

机译：神经元和神经胶质细胞的发育受细胞外因子的顺序规范。

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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.
机译：皮质祖细胞在胚胎发育过程中产生神经元，在出生后产生神经胶质。尽管谱系研究表明多能祖细胞能够产生神经元和神经胶质，但人们对细胞外信号在调节这些细胞的顺序分化中的作用知之甚少。为了研究发育中的皮层中的因素如何影响细胞命运，我们开发了一种皮质切片覆盖测定法，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，在胚皮质切片上培养的胚皮质祖细胞分化为神经元，在产后皮质切片上培养的胚皮质祖细胞分化为神经胶质细胞，表明胚胎祖细胞的命运可能受到发育调控信号的影响。相反，当在胚胎或出生后的皮质切片上培养时，出生后的祖细胞分化为神经胶质细胞。克隆分析表明，产后皮层产生可扩散因子，诱导祖细胞采取神经胶质命运，但以神经元命运为代价。 FGF2和CNTF模仿了产后皮质信号对神经胶质细胞分化的影响，而FGF2和CNTF分别诱导神经胶质命运的规范和最终神经胶质的分化。这些观察结果表明，细胞命运的规范和终末分化可以独立调节，并提示神经胶质细胞发育的增加调节了皮质中神经元和神经胶质的顺序生成。

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