Evolutionary mechanisms controlling brain size and complexity

控制大脑大小和复杂性的进化机制

• 批准号: BB/S001530/1
• 负责人: Corinne Houart
• 金额: $ 87.65万
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FS001530%2F1
• 关键词: Evolutionary; mechanisms; controlling; brain; size

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.

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，但每个区域的相对大小和复杂性在进化过程中存在巨大差异。端脑（形成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、复杂性最高的两个区域，是人类发育和神经退行性疾病中最常见的目标。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最初遗传驱动因素是什么是至关重要的。我们的实验室是早期大脑发育领域的国际领先者，揭示了在大脑形成过程中建立端脑区域的信号机制。我们最近发现，早期脑组织（称为神经板）内信号传导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传导时间的细胞和分子机制，并了解这种时间变化触发的复杂性生成进程。由于控制大脑大小和复杂性的事件是疾病的主要目标，识别它们将导致对疾病机制的新理解和新的候选致病基因。

项目成果

The Birth of the Eye Vesicle: When Fate Decision Equals Morphogenesis.

• DOI: 10.3389/fnins.2018.00087
• 发表时间: 2018
• 期刊: Frontiers in neuroscience
• 影响因子: 4.3
• 作者: Giger FA;Houart C
• 通讯作者: Houart C

Pineal progenitors originate from a non-neural territory limited by FGF signalling.

松果体祖细胞起源于受 FGF 信号传导限制的非神经区域。

• DOI: 10.1242/dev.171405
• 发表时间: 2019
• 期刊: Development (Cambridge, England)
• 作者: Staudt N