Evolutionary mechanisms controlling brain size and complexity

所有脊椎动物的大脑，从鱼类到人类，都是由相同的区域(前脑、中脑和后脑)组成的，但每一个区域的相对大小和复杂性在进化过程中都有巨大的差异。端脑(构成我们大脑半球的前脑的一部分)和小脑(后脑的一部分)是变化最大的两个区域，达到了最高的复杂性，也是人类发育和神经退行性疾病最常见的靶点。因此，了解这种复杂性是如何在发育过程中达到的，以及确保形成像我们这样的正常复杂大脑的初始遗传驱动因素是至关重要的。我们的实验室在早期大脑发育方面处于国际领先地位，揭示了在形成中的大脑中建立端脑区域的信号机制。我们最近发现，在非常早期的脑组织(称为神经板)中，信号发送时间的变化会改变端脑的大小和复杂性。在这里，我们建议确定控制信号时序的细胞和分子机制，并了解由这种时间变化触发的复杂性生成过程。由于控制大脑大小和复杂性的事件是疾病的主要靶点，识别它们将有助于对疾病机制的新理解，并找到新的候选导致疾病的基因。

All vertebrate brains, from fish to human, are formed of the same regions (forebrain, midbrain and hindbrain) but the relative size and complexity of each of these vary tremendously across evolution. The telencephalon (part of the forebrain forming our brain hemispheres) and the cerebellum (part of the hindbrain) are the two areas showing the biggest variation, reaching the highest complexity and being the most common target in human developmental and neurodegenerative disorders. It is therefore of crucial importance to understand how this complexity is reached during development and what are the initial genetic driving elements ensuring formation of a normal complex brain such as ours. Our lab is an international leader in early brain development, having unveiled the signalling mechanism establishing the telencephalic territory inside the forming brain. We very recently found that changes in timing of signalling inside the very early brain tissue (called the neural plate) modify the size and the complexity of the telencephalon. Here, we propose to identify the cellular and molecular mechanisms controlling timing of signalling and understand the complexity-generating progression triggered by this temporal change. As the events controlling brain size and complexity are the prime targets for disorders, identifying them will lead to new understanding of disorder mechanisms and to new candidate disorder-causing genes.