Stable, precise, and reproducible patterning of bicoid and hunchback molecules in the early Drosophila embryo.
Stable, precise, and reproducible patterning of bicoid and hunchback molecules in the early Drosophila embryo.
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DOI：
10.1371/journal.pcbi.1000486
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发表时间：
2009-08
影响因子：
4.3
通讯作者：
Sasai M
中科院分区：
文献类型：
--
作者：
Okabe-Oho Y;Murakami H;Oho S;Sasai M
形态形成分子的精确图谱及其准确读数在胚胎发育中具有重要意义。最近的实验显示了发育中的胚胎中蛋白质的分布，并表明果蝇胚胎中Bicoid形态原的浓度梯度在受精后迅速建立，并通过合胞有丝分裂保持稳定。这种稳定的Bicoid梯度以精确的方式读出，以每个胚胎中具有小波动的方式分布驼背，并且以可重复的方式，具有小的胚胎到胚胎的波动。然而，在嘈杂的细胞过程中，这种稳定、精确和可重复的模式的机制仍然是神秘的。为了解决这些问题，我们开发了早期果蝇胚胎的一维和三维随机模型。模拟结果表明，驼背基因的表达波动主要受Bicoid随机到达驼背增强子的影响。然而，驼背蛋白的缓慢扩散抵消了这种剧烈的波动，导致驼背菌精确的分布模式，而不失去其分布边界的清晰度。输入Bicoid和输出Hunchback的扩散和输运协调速率在抑制胚胎动态结构变化和分子随机扩散引起的波动中起决定性作用，并产生稳定、精确和可复制的Bicoid和Hunchback分布模式。对于发育中的胚胎，精确的、位置特异性的分子过程调控是至关重要的。作为这种调节的机制，被广泛接受的概念是胚胎内分布的调节分子称为“形态因子”。在果蝇胚胎的早期发育阶段，研究得最好的形态因子之一是Bicoid。Bicoid在胚胎前极周围合成，形成指数浓度梯度，在胚胎外围的细胞核中启动目标基因的表达。这在胚胎长度49%左右形成产物蛋白的浓度边界。值得注意的是，胚胎-胚胎在边界位置的变异小于5%。然而，胚胎中的反应本质上应该是嘈杂的，因为涉及的分子数量很少，而且这些反应是由随机扩散的分子控制的。通过过滤强烈的噪声来产生不变的驼背分布的机制仍然是一个谜，在这里我们构建模型来阐明这个问题。随机仿真结果表明，Hunchback的缓慢扩散抵消了强烈的噪声，因此输入Bicoid和输出Hunchback的协调扩散和输移速率对抑制波动起决定性作用。
Precise patterning of morphogen molecules and their accurate reading out are of key importance in embryonic development. Recent experiments have visualized distributions of proteins in developing embryos and shown that the gradient of concentration of Bicoid morphogen in Drosophila embryos is established rapidly after fertilization and remains stable through syncytial mitoses. This stable Bicoid gradient is read out in a precise way to distribute Hunchback with small fluctuations in each embryo and in a reproducible way, with small embryo-to-embryo fluctuation. The mechanisms of such stable, precise, and reproducible patterning through noisy cellular processes, however, still remain mysterious. To address these issues, here we develop the one- and three-dimensional stochastic models of the early Drosophila embryo. The simulated results show that the fluctuation in expression of the hunchback gene is dominated by the random arrival of Bicoid at the hunchback enhancer. Slow diffusion of Hunchback protein, however, averages out this intense fluctuation, leading to the precise patterning of distribution of Hunchback without loss of sharpness of the boundary of its distribution. The coordinated rates of diffusion and transport of input Bicoid and output Hunchback play decisive roles in suppressing fluctuations arising from the dynamical structure change in embryos and those arising from the random diffusion of molecules, and give rise to the stable, precise, and reproducible patterning of Bicoid and Hunchback distributions. For developing embryos, the precise, position-specific regulation of molecular processes is of fatal importance. As the mechanism of such regulation, widely accepted has been the notion of the intraembryonic distribution of regulatory molecules called “morphogens”. One of the best-studied morphogens is Bicoid in the early developmental stage of the Drosophila embryo. Synthesized around the anterior pole of the embryo, Bicoid forms an exponential gradient of concentration to initiate expression of a target gene, hunchback, in nuclei at the periphery of the embryo. This invariably forms a concentration boundary of the product protein Hunchback at around 49% embryo length. Remarkably, the embryo-embryo variability in the boundary position is less than 5%. Reactions in embryos, however, should be intrinsically noisy because the number of molecules involved is small, and those reactions are governed by randomly diffusing molecules. The mechanisms to generate the invariable Hunchback distribution by filtering the intense noise remain mysterious, and here we construct models to shed light on this problem. Stochastic simulations show that the slow diffusion of Hunchback averages out the intense noise, so that the coordinated rates of diffusion and transport of input Bicoid and output Hunchback play decisive roles in suppressing fluctuations.
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影响因子：
64.8
作者：
DRIEVER, W;THOMA, G;NUSSLEINVOLHARD, C
通讯作者：
NUSSLEINVOLHARD, C
DOI：
10.1073/pnas.0509483102
发表时间：
2005-12-20
影响因子：
11.1
作者：
Gregor, T;Bialek, W;Wieschaus, EF
通讯作者：
Wieschaus, EF
DOI：
10.1073/pnas.0807655106
发表时间：
2009-02-10
影响因子：
11.1
作者：
Hecht, Inbal;Rappel, Wouter-Jan;Levine, Herbert
通讯作者：
Levine, Herbert
影响因子：
64.5
作者：
Fowlkes, Charless C.;Luengo Hendriks, Cris L.;Malik, Jitendra
通讯作者：
Malik, Jitendra
影响因子：
8.6
作者：
Bialek, William;Setayeshgar, Sima
通讯作者：
Setayeshgar, Sima