Isolation of a novel platelet-derived growth factor-responsive precursor from the embryonic ventral forebrain
Isolation of a novel platelet-derived growth factor-responsive precursor from the embryonic ventral forebrain
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DOI：
10.1523/jneurosci.3302-04.2004
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发表时间：
2004-12-01
影响因子：
5.3
通讯作者：
Weiss, S
中科院分区：
文献类型：
--
作者：
Chojnacki, A;Weiss, S
少突胶质细胞祖细胞表达血小板衍生生长因子（PDGF）受体-α，并且当仅在PDGF中扩增时，已显示产生少突胶质细胞和星形胶质细胞，但从不产生神经元。最近的证据表明，少突胶质细胞是由一个共同的祖细胞，也产生神经元，但不是星形胶质细胞。我们使用神经球培养系统分离胚胎腹侧前脑，PDGF反应前体（PRPs）。我们报告说，内侧神经节隆起是PRP产生的神经球的来源，后代可以分化成小白蛋白阳性的中间神经元，少突胶质细胞和星形胶质细胞。甲状腺激素和骨形态发生蛋白-2（BMP-2）分别促进少突胶质细胞和神经元的相互排斥的分化，而睫状神经营养因子与BMP-2一起抑制OLIG 2表达并促进星形胶质细胞分化。PRP需要成纤维细胞生长因子-2与PDGF一起维持自我更新，这依赖于音刺猬信号传导。我们提出的证据前脑少突胶质细胞和小白蛋白阳性的中间神经元产生的共同的前体和阐明信号调节的多个分化途径的后代，这一前体。
Oligodendrocyte progenitor cells express platelet-derived growth factor (PDGF) receptor-alpha and, when expanded in PDGF only, have been shown to generate oligodendrocytes and astrocytes but never neurons. Recent evidence suggests that oligodendrocytes are generated by a common progenitor that also generates neurons but not astrocytes. We used the neurosphere culture system to isolate embryonic ventral forebrain, PDGF-responsive precursors (PRPs). We report that the medial ganglionic eminence is the source of PRP-generated neurospheres and that the progeny can differentiate into parvalbumin-positive interneurons, oligodendrocytes, and astrocytes. Thyroid hormone and bone morphogenetic protein-2 (BMP-2) promote the mutually exclusive differentiation of oligodendrocytes and neurons, respectively, whereas ciliary neurotrophic factor acts with BMP-2 to suppress OLIG2 expression and promote astroglial differentiation. PRPs require fibroblast growth factor-2 together with PDGF to maintain self-renewal, which is dependent on sonic hedgehog signaling. We present evidence for forebrain oligodendrocytes and parvalbumin-positive interneurons being generated by a common precursor and elucidate signals regulating the multiple differentiation routes of the progeny of this precursor.