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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Dosage of Fgf8 determines whether cell survival is positively or negatively regulated in the developing forebrain.
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Dosage of Fgf8 determines whether cell survival is positively or negatively regulated in the developing forebrain.

机译：Fgf8的剂量决定了发育中的前脑中细胞存活是正调控还是负调控。

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摘要

FGF8 is known to be an important regulator of forebrain development. Here, we investigated the effects of varying the level of Fgf8 expression in the mouse forebrain. We detected two distinct responses, one that was proportionate with Fgf8 expression and another that was not. The latter response, which led to effects on cell survival, displayed a paradoxical relationship to Fgf8 dosage. Either eliminating or increasing Fgf8 expression increased apoptosis, whereas reducing Fgf8 expression had the opposite effect. To explain these counterintuitive observations, we suggest that an FGF8-dependent cell-survival pathway is negatively regulated by intracellular inhibitors produced in proportion to FGF8 concentration. Our data provide insight into the function of FGF8 in forebrain development and underscore the value of using multiple alleles and different experimental approaches to unravel the complexities of gene function in vertebrate development.
机译：众所周知，FGF8是前脑发育的重要调节剂。在这里，我们研究了在小鼠前脑中改变Fgf8表达水平的影响。我们检测到两种不同的反应，一种与Fgf8表达成比例，另一种与Fgf8表达成比例。后者的反应导致对细胞存活的影响，与Fgf8剂量显示出矛盾的关系。消除或增加Fgf8表达可增加凋亡，而减少Fgf8表达则具有相反的作用。为了解释这些违反直觉的发现，我们建议FGF8依赖的细胞存活途径受到与FGF8浓度成比例产生的细胞内抑制剂的负调控。我们的数据提供了对FGF8在前脑发育中的功能的深入了解，并强调了使用多个等位基因和不同实验方法揭示脊椎动物发育中基因功能复杂性的价值。

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