Computational insights into Caenorhabditis elegans vulval development
Computational insights into Caenorhabditis elegans vulval development
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DOI：
10.1073/pnas.0409433102
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发表时间：
2005-02-08
影响因子：
11.1
通讯作者：
Harel, D
中科院分区：
文献类型：
--
作者：
Fisher, J;Piterman, N;Harel, D
对秀丽线虫外阴发育的研究为动物发育过程中的模式形成提供了一个范例。这六个外阴前体细胞的命运是由激活EGF受体有丝分裂原激活的PK信号通路的诱导信号(指定初级命运)和由Lin-12/Notch介导的横向信号(指定次级命运)的联合作用决定的。在这里，我们使用为复杂反应系统的工程设计的方法来模拟生物系统。我们选择了状态图的视觉形式主义，并用它来形式化Sternberg和Horvitz 1989年的模型[Sternberg，P.W.&Horvitz，H.R.(11989)Cell 58,679-693]，该模型形成了我们目前对这两个信号通路之间相互作用的理解的基础。我们模型的构建和执行表明，不同水平的诱导信号诱导了EGF受体丝裂原激活的PK通路的时间分级反应，并明确了这种时间反应的重要性。我们的模型还表明，在横向规范过程中存在另一种机制，该机制阻止邻近的外阴前体细胞承担主要命运。
Studies of Caenorhabditis elegans vulval development provide a paradigm for pattern formation during animal development. The fates of the six vulval precursor cells are specified by the combined action of an inductive signal that activates the EGF receptor mitogen-activated PK signaling pathway (specifying a primary fate) and a lateral signal mediated by LIN-12/Notch (specifying a secondary fate). Here we use methods devised for the engineering of complex reactive systems to model a biological system. We have chosen the visual formalism of statecharts and use it to formalize Sternberg and Horvitz's 1989 model [Sternberg, P. W. & Horvitz, H. R. (11989) Cell 58, 679-693], which forms the basis for our current understanding of the interaction between these two signaling pathways. The construction and execution of our model suggest that different levels of the inductive signal induce a temporally graded response of the EGF receptor mitogen-activated PK pathway and make explicit the importance of this temporal response. Our model also suggests the existence of an additional mechanism operating during lateral specification that prohibits neighboring vulval precursor cells from assuming the primary fate.