Modeling of the dorsal gradient across species reveals interaction between embryo morphology and Toll signaling pathway during evolution.
Modeling of the dorsal gradient across species reveals interaction between embryo morphology and Toll signaling pathway during evolution.
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DOI：
10.1371/journal.pcbi.1003807
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发表时间：
2014-08
影响因子：
4.3
通讯作者：
Mizutani CM
中科院分区：
文献类型：
--
作者：
Ambrosi P;Chahda JS;Koslen HR;Chiel HJ;Mizutani CM
形态发生梯度是至关重要的分配细胞的命运在不同大小的胚胎内和跨密切相关的物种。我们以前发现，母体NF-κB/背侧（DI）梯度在果蝇物种中获得了不同的形状，这导致沿着背腹轴的不均匀缩放的胚层和神经外胚层边界的重新定位。在这里，我们结合实验和数学建模来研究哪些因素可能导致了这种梯度的快速进化变化。为此，我们修改了以前开发的模型，采用微分方程的主要生化相互作用的Toll（T1）信号通路，调节D1核运输。原始模型模拟结果与D.黑腹菌野生型，但不是突变体条件。为了拓宽该模型的适用性并探测梯度分布的进化变化，我们调整了一组19个独立参数以再现三个量化的实验条件（即DI水平降低，核大小和密度增加或减少）。我们接下来搜索再现物种特异性Dl梯度的最相关参数。我们表明，调整参数相对于形态性状（即胚胎直径，核大小和密度）单独是不足以重现物种D1梯度。由于模型模拟的T1途径的组分是快速演变的，我们接下来询问与T1相关的哪些参数将最有效地再现这些梯度并鉴定特定子集。敏感性分析揭示了上述两个快速进化性状之间存在非线性相互作用，即胚胎形态学变化和T1途径组分。我们的建模进一步表明，在密切相关的黑腹亚群谱系中观察到的不同D1梯度形状可能是由T1途径组分中的类似序列修饰引起的，这与它们的系统发育关系一致。胚胎大小在密切相关的物种之间差异很大。组织规格如何在不同物种的发育胚胎中缩放或修改是发育生物学中正在进行的研究。在这里，我们问胚胎形态和特定的分子途径如何通过改变形态发生素的分布来影响组织规格。形态发生素是形成以剂量依赖性方式调节基因表达模式的梯度的分子，其导致组织特化，因此是进化的主要目标，以调节或维持与总体胚胎大小相关的组织比例。我们使用了一个数学模型，以确定影响的背形态梯度，负责图案化的果蝇果蝇胚胎的背腹轴的分布的因素。我们从突变条件和不同种类的果蝇中获得了实验数据来校准我们的模型，并发现胚胎形态和Toll通路调节之间的相互作用，该通路调节Dorsal梯度。此外，该模型预测，密切相关的物种共享Toll途径组件中的类似修改，导致其物种特异性梯度形状，这是支持的组件Dorsal和仙人掌的种间氨基酸比较。
Morphogenetic gradients are essential to allocate cell fates in embryos of varying sizes within and across closely related species. We previously showed that the maternal NF-κB/Dorsal (Dl) gradient has acquired different shapes in Drosophila species, which result in unequally scaled germ layers along the dorso-ventral axis and the repositioning of the neuroectodermal borders. Here we combined experimentation and mathematical modeling to investigate which factors might have contributed to the fast evolutionary changes of this gradient. To this end, we modified a previously developed model that employs differential equations of the main biochemical interactions of the Toll (Tl) signaling pathway, which regulates Dl nuclear transport. The original model simulations fit well the D. melanogaster wild type, but not mutant conditions. To broaden the applicability of this model and probe evolutionary changes in gradient distributions, we adjusted a set of 19 independent parameters to reproduce three quantified experimental conditions (i.e. Dl levels lowered, nuclear size and density increased or decreased). We next searched for the most relevant parameters that reproduce the species-specific Dl gradients. We show that adjusting parameters relative to morphological traits (i.e. embryo diameter, nuclear size and density) alone is not sufficient to reproduce the species Dl gradients. Since components of the Tl pathway simulated by the model are fast-evolving, we next asked which parameters related to Tl would most effectively reproduce these gradients and identified a particular subset. A sensitivity analysis reveals the existence of nonlinear interactions between the two fast-evolving traits tested above, namely the embryonic morphological changes and Tl pathway components. Our modeling further suggests that distinct Dl gradient shapes observed in closely related melanogaster sub-group lineages may be caused by similar sequence modifications in Tl pathway components, which are in agreement with their phylogenetic relationships. Embryo size can vary greatly among closely related species. How tissue specification either scales or is modified in the developing embryo in different species is an ongoing investigation in developmental biology. Here we asked how embryo morphology and specific molecular pathways influence tissue specification by altering the distribution of morphogens. Morphogens are molecules that form gradients that regulate gene expression patterns in a dosage-dependent fashion that result in tissue specification, and therefore are a prime target for evolution in order to adjust or maintain tissue proportions in relation to overall embryo size. We used a mathematical model to identify factors that influence the distribution of the Dorsal morphogen gradient that is responsible for patterning the dorsal-ventral axis of the Drosophila fruit fly embryo. We obtained experimental data from mutant conditions and different species of Drosophila to calibrate our model and found an interaction between embryo morphology and regulation of the Toll pathway, which regulates the Dorsal gradient. Furthermore, the model predicts that closely related species share similar modifications in Toll pathway components resulting in their species-specific gradient shapes, which are supported by interspecies amino acid comparison of the components Dorsal and Cactus.
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影响因子：
64.8
作者：
Clark, Andrew G.;Eisen, Michael B.;MacCallum, Iain
通讯作者：
MacCallum, Iain
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
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：
4.5
作者：
Fowlkes CC;Eckenrode KB;Bragdon MD;Meyer M;Wunderlich Z;Simirenko L;Luengo Hendriks CL;Keränen SV;Henriquez C;Knowles DW;Biggin MD;Eisen MB;DePace AH
通讯作者：
DePace AH
影响因子：
9.2
作者：
Chahda, Juan Sebastian;Sousa-Neves, Rui;Mizutani, Claudia Mieko
通讯作者：
Mizutani, Claudia Mieko