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首页> 外文期刊>The Journal of Neuroscience: The Official Journal of the Society for Neuroscience >Transforming growth factor-beta(s) are essential for the development of midbrain dopaminergic neurons in vitro and in vivo.
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Transforming growth factor-beta(s) are essential for the development of midbrain dopaminergic neurons in vitro and in vivo.

机译：转化生长因子-β对于中脑多巴胺能神经元的体外和体内发育至关重要。

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摘要

Development of midbrain dopaminergic neurons is known to depend on inductive signals derived from the ventral midline, including Sonic hedgehog (Shh) as one of the identified molecules. Here we show that in addition to Shh, transforming growth factor (TGF)-beta is required for both induction and survival of ventrally located midbrain dopaminergic neurons. Like Shh, TGF-beta is expressed in early embryonic structures such as notochord and floor plate, as well as in the area where midbrain dopaminergic neurons are developing. Treatment of cells dissociated from the rat embryonic day (E) 12 midbrain floor with TGF-beta significantly increases the number of tyrosine hydroxylase (TH)-positive dopaminergic neurons within 24 hr. Neutralization of TGF-beta in vitro completely abolishes the induction of dopaminergic neurons. In the absence of TGF-beta, Shh cannot induce TH-positive neurons, and vice versa, neutralizing endogenous Shh abolishes the capacity of TGF-beta to induce dopaminergic neurons in vitro. Furthermore, neutralization of TGF-beta in vivo during chick E2-7 but not E4-7 resulted in a significant reduction in TH-positive neurons in the ventral midbrain floor but not in the locus coeruleus or diencephalon, which suggests that the TGF-beta is required for the induction of mesencephalic dopaminergic neurons with a critical time period at E2/E3. Furthermore, neutralization of TGF-beta between E6 and 10, a time period during maturation of mesencephalic dopaminergic neurons when no further inductive cues are required, also resulted in a significant loss of dopaminergic neurons, suggesting that TGF-beta is required for the promotion of survival of ventral midbrain dopaminergic neurons as well. Together, our results identify TGF-beta as an essential mediator for the induction and maintenance of midbrain dopaminergic neurons.
机译：已知中脑多巴胺能神经元的发育取决于源自腹中线的感应信号，包括作为已鉴定分子之一的Sonic刺猬（Shh）。在这里，我们显示除Shh之外，腹侧中脑多巴胺能神经元的诱导和存活都需要转化生长因子（TGF）-β。像Shh一样，TGF-β在早期胚胎结构（如脊索和底板）以及中脑多巴胺能神经元发育区域表达。用TGF-β处理从大鼠胚胎第（E）12天中脑底部离解的细胞会在24小时内显着增加酪氨酸羟化酶（TH）阳性多巴胺能神经元的数量。在体外中和TGF-β完全消除了对多巴胺能神经元的诱导。在没有TGF-β的情况下，Shh无法诱导TH阳性神经元，反之亦然，中和内源性Shh消除了TGF-β在体外诱导多巴胺能神经元的能力。此外，在小鸡E2-7而非E4-7期间体内中和TGF-β会导致腹侧中脑底而不是蓝斑或中脑的TH阳性神经元显着减少，这表明TGF-β在E2 / E3的关键时期诱导中脑多巴胺能神经元是必需的。此外，在中脑多巴胺能神经元成熟期间不需要进一步的诱导线索时，E6和10之间的TGF-β中和也导致多巴胺能神经元的大量损失，这表明促进TGF-β促进腹中脑多巴胺能神经元的存活率也是如此。总之，我们的结果确定TGF-β是诱导和维持中脑多巴胺能神经元的重要介体。

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