Aegerter-Wilmsen Tinri, Aegerter Christof M, Hafen Ernst, Basler Konrad
Zoological Institute, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
Mech Dev. 2007 Apr;124(4):318-26. doi: 10.1016/j.mod.2006.12.005. Epub 2006 Dec 29.
For animal development it is necessary that organs stop growing after they reach a certain size. However, it is still largely unknown how this termination of growth is regulated. The wing imaginal disc of Drosophila serves as a commonly used model system to study the regulation of growth. Paradoxically, it has been observed that growth occurs uniformly throughout the disc, even though Decapentaplegic (Dpp), a key inducer of growth, forms a gradient. Here, we present a model for the control of growth in the wing imaginal disc, which can account for the uniform occurrence and termination of growth. A central feature of the model is that net growth is not only regulated by growth factors, but by mechanical forces as well. According to the model, growth factors like Dpp induce growth in the center of the disc, which subsequently causes a tangential stretching of surrounding peripheral regions. Above a certain threshold, this stretching stimulates growth in these peripheral regions. Since the stretching is not completely compensated for by the induced growth, the peripheral regions will compress the center of the disc, leading to an inhibition of growth in the center. The larger the disc, the stronger this compression becomes and hence the stronger the inhibiting effect. Growth ceases when the growth factors can no longer overcome this inhibition. With numerical simulations we show that the model indeed yields uniform growth. Furthermore, the model can also account for other experimental data on growth in the wing disc.
对于动物发育而言,器官在达到一定大小后停止生长是必要的。然而,这种生长终止是如何被调控的,在很大程度上仍然未知。果蝇的翅成虫盘是研究生长调控常用的模型系统。矛盾的是,尽管生长的关键诱导因子——骨形态发生蛋白(Dpp)形成了梯度,但已观察到整个翅成虫盘的生长是均匀发生的。在此,我们提出了一个翅成虫盘生长控制模型,该模型可以解释生长的均匀发生和终止。该模型的一个核心特征是净生长不仅受生长因子调控,还受机械力调控。根据该模型,像Dpp这样的生长因子在翅成虫盘中心诱导生长,这随后导致周围周边区域的切向拉伸。超过一定阈值后,这种拉伸会刺激这些周边区域的生长。由于诱导生长并不能完全补偿拉伸,周边区域会压缩翅成虫盘的中心,导致中心生长受到抑制。翅成虫盘越大,这种压缩就越强,因此抑制作用也越强。当生长因子无法再克服这种抑制时,生长就会停止。通过数值模拟,我们表明该模型确实能产生均匀生长。此外,该模型还能解释翅成虫盘生长的其他实验数据。