Sonic hedgehog-expressing cells in the developing limb measure time by an intrinsic cell cycle clock.
Sonic hedgehog-expressing cells in the developing limb measure time by an intrinsic cell cycle clock.
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DOI：
10.1038/ncomms5230
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发表时间：
2014-07-08
影响因子：
16.6
通讯作者：
Towers, Matthew
中科院分区：
文献类型：
--
作者：
Chinnaiya, Kavitha;Tickle, Cheryll;Towers, Matthew
如何衡量时间是发育生物学中一个经久不衰的问题。体细胞发生和肢体发育的经典模型涉及内在的细胞周期时钟，但它们的存在仍然存在争议。在这里，我们展示了小鸡肢芽极化区细胞内固有的细胞周期时钟乘以Sonic hedgehog （Shh）表达的持续时间，其编码指定横跨前后轴（拇指到小指）的手指模式的形态原。当极化区细胞脱离维甲酸信号传导范围时，这个时钟开始计时。我们发现细胞周期时钟的Shh转录时间可以重置，从而揭示了一种胚胎形式的自我更新。相反，前后位值不能重置，这可能是对手指再生的重要限制。我们的发现提供了一个内在的细胞周期定时器控制的持续时间和模式活动的主要胚胎信号中心的第一个证据。在脊椎动物肢体形成过程中，形态原Sonic Hedgehog （Shh）由极化区（ZPA）的细胞产生。在这里，作者通过鸡胚胎移植实验表明，ZPA细胞Shh表达的持续时间是由细胞周期时钟决定的，这个周期时钟可以启动，也可以通过维甲酸信号传导的变化来重置。
How time is measured is an enduring issue in developmental biology. Classical models of somitogenesis and limb development implicated intrinsic cell cycle clocks, but their existence remains controversial. Here we show that an intrinsic cell cycle clock in polarizing region cells of the chick limb bud times the duration of Sonic hedgehog (Shh) expression, which encodes the morphogen specifying digit pattern across the antero-posterior axis (thumb to little finger). Timing by this clock starts when polarizing region cells fall out of range of retinoic acid signalling. We found that timing of Shh transcription by the cell cycle clock can be reset, thus revealing an embryonic form of self-renewal. In contrast, antero-posterior positional values cannot be reset, suggesting that this may be an important constraint on digit regeneration. Our findings provide the first evidence for an intrinsic cell cycle timer controlling duration and patterning activity of a major embryonic signalling centre. During vertebrate limb patterning the morphogen Sonic Hedgehog (Shh) is produced by cells of the polarizing region (ZPA). Here, the authors show, using chick embryo grafting experiments, that the duration of Shh expression by ZPA cells is defined by a cell cycle clock that is started and can also be reset by changes in retinoic acid signalling.
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