Somitogenesis clock-wave initiation requires differential decay and multiple binding sites for clock protein.
Somitogenesis clock-wave initiation requires differential decay and multiple binding sites for clock protein.
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DOI：
10.1371/journal.pcbi.1000728
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发表时间：
2010-04-01
影响因子：
4.3
通讯作者：
Gedeon T
中科院分区：
文献类型：
--
作者：
Campanelli M;Gedeon T
躯体发生是所有脊椎动物胚胎共同的一个过程，在这个过程中，体细胞块从体前中胚层（PSM）产生，为躯干和尾巴的发育奠定了基础。一些小体形成于起源于尾芽并向后扫过PSM的周期性基因表达的传递波的尾迹中。先前的研究表明，这种波是由一种影响时钟基因表达振荡速率的时空梯度控制蛋白引起的。通过最小构造的数学模型，我们研究了两种控制机制对这种基因表达波的初始形成的贡献。我们测试了四种具有一个或两个时钟蛋白转录结合位点的生物动机模型情景，以及时钟蛋白单体和二聚体的不同衰减率。我们研究了波浪形成对多个模型参数的敏感性和对细胞群体异质性的鲁棒性。我们发现只有具有多个结合位点和不同衰减率的模型才能重现实验观察到的波形。我们的研究结果表明，实验观察到的躯体发生波起始的特征限制了潜在的遗传控制机制。脊柱是所有脊椎动物的特征结构。单独的椎骨，连同肋骨和附着的肌肉，由重复的胚胎结构发育而来，称为体。体体模式在胚胎发育过程中形成。我们知道这个过程使用周期性的基因表达（一种生物分子“时钟”）来产生这种模式，但我们并不确切地知道这种表达是如何在细胞内控制并在多个细胞之间协调的。我们提出了一个数学模型，结合实验证实的体细胞发生的特征。然后，我们测试了四种可能控制时钟的不同机制，并询问模型模拟和实验观察之间的比较是否可以选择最佳模型，从而建议如何控制时钟。我们发现，具有多个DNA结合位点和不同蛋白质衰变率的模型情景最能再现实验观察结果。因为这些发现可以通过实验来验证，我们的结果应该有助于指导未来的实验。
Somitogenesis is a process common to all vertebrate embryos in which repeated blocks of cells arise from the presomitic mesoderm (PSM) to lay a foundational pattern for trunk and tail development. Somites form in the wake of passing waves of periodic gene expression that originate in the tailbud and sweep posteriorly across the PSM. Previous work has suggested that the waves result from a spatiotemporally graded control protein that affects the oscillation rate of clock-gene expression. With a minimally constructed mathematical model, we study the contribution of two control mechanisms to the initial formation of this gene-expression wave. We test four biologically motivated model scenarios with either one or two clock protein transcription binding sites, and with or without differential decay rates for clock protein monomers and dimers. We examine the sensitivity of wave formation with respect to multiple model parameters and robustness to heterogeneity in cell population. We find that only a model with both multiple binding sites and differential decay rates is able to reproduce experimentally observed waveforms. Our results show that the experimentally observed characteristics of somitogenesis wave initiation constrain the underlying genetic control mechanisms. The vertebral column is a characteristic structure of all vertebrates. Individual vertebrae, together with ribs and attached muscles, develop from repeated embryonic structures called somites. The somite pattern forms in the embryo during somitogenesis. We know that this process uses periodic gene expression (a biomolecular “clock”) to generate the pattern, but we do not know precisely how this expression is controlled within the cell and coordinated across multiple cells. We propose a mathematical model that incorporates experimentally confirmed features of somitogenesis. We then test four different mechanisms that may control the clock and ask if the comparison between model simulations and experimental observation can select the best model and thus suggest how the clock is controlled. We find that the model scenario with both multiple DNA binding sites and differential protein decay rates is best able to reproduce experimental observations. Because these findings can be tested experimentally, our results should help guide future experiments.
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影响因子：
2.5
作者：
Goldbeter, Albert;Gonze, Didier;Pourquie, Olivier
通讯作者：
Pourquie, Olivier
影响因子：
64.8
作者：
Dubrulle, J;Pourquié, O
通讯作者：
Pourquié, O
影响因子：
4.3
作者：
Baker, R. E.;Maini, P. K.
通讯作者：
Maini, P. K.
影响因子：
--
作者：
Baker, Ruth E.;Schnell, Santiago
通讯作者：
Schnell, Santiago
DOI：
10.1073/pnas.0409553102
发表时间：
2005-07-05
影响因子：
11.1
作者：
Buchler, NE;Gerland, U;Hwa, T
通讯作者：
Hwa, T