Modeling craniofacial development reveals spatiotemporal constraints on robust patterning of the mandibular arch.
Modeling craniofacial development reveals spatiotemporal constraints on robust patterning of the mandibular arch.
复制标题
DOI：
10.1371/journal.pcbi.1006569
复制
发表时间：
2018-11
影响因子：
4.3
通讯作者：
Schilling TF
中科院分区：
文献类型：
--
作者：
Meinecke L;Sharma PP;Du H;Zhang L;Nie Q;Schilling TF
当面对组织生长和基因表达的随机波动(噪声)时，如何准确地形成模式？下颌弓的背腹(D-V)模式通过骨形态发生蛋白(BMP)、内皮素-1(Edn1)和Notch信号的组合来指定上颌和下颌骨的骨骼元素，并且该系统是高度健壮的。我们将斑马鱼早期D-V基因表达的纳米线实验与牙弓发育的实时成像相结合，构建了D-V下颌图案网络的计算模型。该模型概括了已发表的ARCH发育过程中的遗传扰动。模式对BMP信号的变化最敏感，基因表达的时间顺序调节模式网络对噪声的反应。因此，我们的综合系统生物学方法揭示了对颅面发育至关重要的复杂信号系统的非直观特征，包括对基因表达时序和随机性在信号和基因调控中的作用的新见解。身体的正常发育需要在细胞形成不同结构的区域之间形成边界，这些边界需要在空间中适当地组织起来。即使在细胞移动、分裂和存在所有生化过程中固有的噪音的情况下，这也必须准确地发生。我们以上、下颌骨发育为模型来研究边界的形成。在这项工作中，我们结合详细的实验测量和计算模型来研究基因表达的时序在组织空间边界中所起的作用，并发现不同的基因表达顺序在边界定位的精确度和精确度之间进行了权衡。
How does pattern formation occur accurately when confronted with tissue growth and stochastic fluctuations (noise) in gene expression? Dorso-ventral (D-V) patterning of the mandibular arch specifies upper versus lower jaw skeletal elements through a combination of Bone morphogenetic protein (Bmp), Endothelin-1 (Edn1), and Notch signaling, and this system is highly robust. We combine NanoString experiments of early D-V gene expression with live imaging of arch development in zebrafish to construct a computational model of the D-V mandibular patterning network. The model recapitulates published genetic perturbations in arch development. Patterning is most sensitive to changes in Bmp signaling, and the temporal order of gene expression modulates the response of the patterning network to noise. Thus, our integrated systems biology approach reveals non-intuitive features of the complex signaling system crucial for craniofacial development, including novel insights into roles of gene expression timing and stochasticity in signaling and gene regulation. Proper development of the body requires boundaries to form between regions in which cells will form different structures, and these boundaries need to be properly organized in space. This must occur accurately even in moving, dividing cells and in the presence of the noise that is inherent in all biochemical processes. We use development of the upper and lower jaw as a model to study boundary formation. In this work, we combine detailed experimental measurements with computational modeling to investigate the role the timing of gene expression plays in organizing spatial boundaries, and find that the different orders of gene expression navigate a tradeoff between precision and accuracy in boundary positioning.
登录
查看更多内容
影响因子：
2
作者：
Clouthier, David E.;Garcia, Elvin;Schilling, Thomas F.
通讯作者：
Schilling, Thomas F.
影响因子：
30.8
作者：
Economou, Andrew D.;Ohazama, Atsushi;Porntaveetus, Thantrira;Sharpe, Paul T.;Kondo, Shigeru;Basson, M. Albert;Gritli-Linde, Amel;Cobourne, Martyn T.;Green, Jeremy B. A.
通讯作者：
Green, Jeremy B. A.
影响因子：
4.5
作者：
Das A;Crump JG
通讯作者：
Crump JG
影响因子：
11.8
作者：
Barske, Lindsey;Rataud, Pauline;Crump, J. Gage
通讯作者：
Crump, J. Gage
影响因子：
2.7
作者：
Hindmarsh, AC;Brown, PN;Woodward, CS
通讯作者：
Woodward, CS