Organism-scale modeling of early Drosophila patterning via bone morphogenetic proteins.-猫眼课题宝

DOI：

10.1016/j.devcel.2010.01.006

发表时间：

2010-02-16

期刊：

DEVELOPMENTAL CELL

影响因子：

11.8

通讯作者：

中科院分区：

生物学1区

文献类型：

作者：

Ulmulis, David M.;Shimmi, Osamu;O'Connor, Michael B.;Othmer, Hans G.

来源链接：

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2848394/?report=classic

图像采集和信息学技术的进步导致了生物体尺度的基因表达和蛋白质分布的时空图谱。为了最大限度地利用这些信息来研究发展过程，需要新一代的数学模型来进行发现和假设检验。在这里，我们开发了一个数据驱动的，几何精确的，早期果蝇胚胎骨形态发生蛋白（BMP）介导的图案模型。我们测试了9种不同的机制，反馈信号转导，8种几何形状和基因表达的组合，和两个规模不变的机制，他们的能力，在野生型和突变体胚胎中重现正确的BMP信号输出。我们发现，一个模型的基础上分泌的BMP结合蛋白的正反馈，再加上实验测量的胚胎几何形状，提供了最好的协议与人口平均图像数据。我们的研究结果表明，使用生物图像来构建和优化3D模型，为指导组织图案形成的机制提供了重要的新见解。

Advances in image acquisition and informatics technology have led to organism-scale spatio-temporal atlases of gene expression and protein distributions. To maximize the utility of this information for the study of developmental processes, a new generation of mathematical models is needed for discovery and hypothesis testing. Here we develop a data-driven, geometrically-accurate, model of early Drosophila embryonic bone morphogenetic protein (BMP)-mediated patterning. We tested nine different mechanisms for signal transduction with feedback, eight combinations of geometry and gene expression prepatterns, and two scale-invariance mechanisms for their ability to reproduce proper BMP signaling output in wild-type and mutant embryos. We found that a model based on positive feedback of a secreted BMP binding protein, coupled with the experimentally-measured embryo geometry, provides the best agreement with population-mean image data. Our results demonstrate that using bioimages to build and optimize a 3D model provides significant new insights into mechanisms that guide tissue patterning.