Elucidating the mechanism of organ size control by KLU-dependent intercellular signalling

雏菊总是比向日葵小，而牛总是比羊大。正如这些例子所强调的那样，植物和动物生长到特定物种特有的大小，这是由它们的发育遗传程序控制的。了解生物体及其器官的大小是基础生物学的一个重要目标，这将允许合理地操纵经济相关物种的生长和大小。尽管已经确定了几个影响器官大小的基因，但正在发育的器官如何测量其大小的根本问题仍然没有解决。我们最近已经证明，器官边缘的细胞在决定其大小方面起着特别重要的作用。这些边缘细胞产生一种小分子，作为一种可移动的生长调节器，可以进入器官并维持细胞增殖。由于纯粹的几何原因，器官的边缘比整个区域生长得更慢，这表明随着器官大小的增加，生长调节器被稀释。这为通过这种生长调节剂的浓度测量器官大小提供了一种简单的方法。在这种观点下，一旦生长调节剂的浓度降到临界值以下，当器官达到一定大小时，细胞增殖就会停止。这个模型类似于目前关于如何控制动物器官大小的想法，例如苍蝇的翅膀，这表明最终植物和动物使用相同的原理来测量器官的大小。这个假定信号的产生需要Kluh(Klu)基因的活性，Kluh(Klu)基因只在器官的边缘活跃，为进一步研究植物器官生长的控制提供了一个很好的切入点。这项建议的目的是更详细地了解依赖Klu的生长调节因子如何控制器官大小。为此，我们将重点解决四个问题。1.依赖于Klu的增长监管机构的流动性有多大？上面提出的测量器官大小的模型假设生长调节剂是高度流动的我们将通过监测细胞对生长调节剂的反应来测试这一点，看看在本地启动生产后它如何在器官中传播。2.是否有生产活性生长调节剂的蛋白质装配线？我们发现，当Klu基因被激活时，许多相关的、相似的蛋白质被激活。这表明，这些其他蛋白质也参与了生长调节剂的形成或分解。我们将通过培育含有过多或过少这些蛋白质的植物并研究其对器官大小的影响来测试这一点。3.Klu蛋白修饰哪些小分子(S)？作为寻找活性生长调节剂的第一步，我们将通过比较KLU开启前后不同小分子的数量来鉴定被KLU修饰的小分子(S)。4.产生或感知生长调节剂还需要哪些其他基因？我们将搜索不再对生长调节剂做出反应的植物，然后利用这些植物来识别感知信号所需的其他基因。总而言之，这些研究应该会对正在生长的器官如何测量其大小并决定何时适可而止产生重要的见解。

Daisies are always smaller than sunflowers, while cows are always larger than sheep. As these examples highlight, plants and animals grow to characteristic, species-specific sizes that are controlled by their developmental genetic programmes. Understanding how the size of organisms and their organs is determined is an important goal of basic biology, which will allow the rational manipulation of growth and size in economically relevant species. Although several genes have been identified that influence organ size, the fundamental problem of how a growing organ can measure its size is still unresolved. We have recently shown that the cells at the margins of an organ play a particularly important part in determining its size. These marginal cells produce a small molecule acting as a mobile growth regulator that can move into the organ and maintain cell proliferation. For purely geometric reasons the margin of the organ grows more slowly than the overall area, suggesting that the growth regulator is diluted as the organ increases in size. This offers a simple means for measuring organ size via the concentration of this growth regulator. In this view, cell proliferation arrests, once the concentration of the growth regulator falls below a critical value when the organ reaches a certain size. This model is similar to current ideas about how the size of animal organs, for example fly wings, is controlled, suggesting that ultimately plants and animals use the same principle to measure organ size. The production of this presumed signal requires the activity of the KLUH (KLU) gene, which is only active at the margins of the organs and provides an excellent point of entry for further studying the control of plant organ growth. The aim of this proposal is to gain a more detailed understanding of how the KLU-dependent growth regulator controls organ size. To this end, we will focus on four questions. 1. How mobile is the KLU-dependent growth regulator? The model proposed above for measuring organ size assumes that the growth regulator is highly mobile We will test this by monitoring the response of cells to the growth regulator, to see how it spreads in organs after its production is switched on locally. 2. Is there an assembly line of proteins to make the active growth regulator? We have found that a number of related, similar proteins are activated when the KLU gene is switched on. This suggests that these other proteins are also involved in making or breaking down the growth regulator. We will test this by generating plants that either have too much or too little of these proteins and studying the effect on organ size. 3. Which small molecule(s) are modified by the KLU protein? As a first step to finding the active growth regulator, we will identify the small molecule(s) that are modified by KLU, by comparing the amounts of different small molecules before and after KLU has been switched on. 4. Which other genes are necessary to generate or perceive the growth regulator? We will search for plants that can no longer respond to the growth regulator and then use these to identify additional genes necessary to perceive the signal. Together, these studies should yield important insights into how growing organs measure their size and decide when enough is enough.