Integrating force-sensing and signaling pathways in a model for the regulation of wing imaginal disc size
Integrating force-sensing and signaling pathways in a model for the regulation of wing imaginal disc size
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DOI：
10.1242/dev.082800
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发表时间：
2012-09-01
期刊：
影响因子：
4.6
通讯作者：
Basler, Konrad
中科院分区：
文献类型：
--
作者：
Aegerter-Wilmsen, Tinri;Heimlicher, Maria B.;Basler, Konrad
器官大小的调节是发育生物学中一个尚未解决的主要问题。果蝇的翅盘是研究这一问题的一个广泛使用的模型系统。已经提出了几种机制对最终尺寸产生影响，但它们要么与实验数据相矛盾，要么无法解释一些关键的实验观察结果，因此可能缺少关键要素。我们已经建立了一个调控网络，整合了实验证实的分子相互作用的基础上其他可用的模型。此外，该网络包括机械力和特定的生长调节剂之间的假设的相互作用，导致在概念上结合现有模型的元素的大小调节机制，并且可以理解的压缩梯度模型。根据这个模型，在生长过程中，椎间盘中心的压缩增加。一旦椎间盘中心的压缩水平达到一定阈值，并且椎间盘其余部分的压缩梯度下降到一定水平以下，生长就会停止。我们的模型可以解释生长终止以及矛盾的观察，即生长均匀地发生在存在的生长因子梯度和不均匀地存在的均匀的生长因子分布。此外，它还可以解释其他支持或反对其他模型的实验观察结果。该模型还对发育中的细胞形状和大小的分布做出了具体的预测，我们能够通过实验证实这一点。
The regulation of organ size constitutes a major unsolved question in developmental biology. The wing imaginal disc of Drosophila serves as a widely used model system to study this question. Several mechanisms have been proposed to have an impact on final size, but they are either contradicted by experimental data or they cannot explain a number of key experimental observations and may thus be missing crucial elements. We have modeled a regulatory network that integrates the experimentally confirmed molecular interactions underlying other available models. Furthermore, the network includes hypothetical interactions between mechanical forces and specific growth regulators, leading to a size regulation mechanism that conceptually combines elements of existing models, and can be understood in terms of a compression gradient model. According to this model, compression increases in the center of the disc during growth. Growth stops once compression levels in the disc center reach a certain threshold and the compression gradient drops below a certain level in the rest of the disc. Our model can account for growth termination as well as for the paradoxical observation that growth occurs uniformly in the presence of a growth factor gradient and non-uniformly in the presence of a uniform growth factor distribution. Furthermore, it can account for other experimental observations that argue either in favor or against other models. The model also makes specific predictions about the distribution of cell shape and size in the developing disc, which we were able to confirm experimentally.