MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Cambridge, UK.
Princeton Neuroscience Institute, Princeton University, Princeton, NJ, USA.
Nature. 2024 Jun;630(8017):596-608. doi: 10.1038/s41586-024-07521-x. Epub 2024 Jun 19.
The evolution of the modern human brain was accompanied by distinct molecular and cellular specializations, which underpin our diverse cognitive abilities but also increase our susceptibility to neurological diseases. These features, some specific to humans and others shared with related species, manifest during different stages of brain development. In this multi-stage process, neural stem cells proliferate to produce a large and diverse progenitor pool, giving rise to excitatory or inhibitory neurons that integrate into circuits during further maturation. This process unfolds over varying time scales across species and has progressively become slower in the human lineage, with differences in tempo correlating with differences in brain size, cell number and diversity, and connectivity. Here we introduce the terms 'bradychrony' and 'tachycrony' to describe slowed and accelerated developmental tempos, respectively. We review how recent technical advances across disciplines, including advanced engineering of in vitro models, functional comparative genetics and high-throughput single-cell profiling, are leading to a deeper understanding of how specializations of the human brain arise during bradychronic neurodevelopment. Emerging insights point to a central role for genetics, gene-regulatory networks, cellular innovations and developmental tempo, which together contribute to the establishment of human specializations during various stages of neurodevelopment and at different points in evolution.
人类大脑的进化伴随着明显的分子和细胞特化，这些特化为我们多样化的认知能力提供了基础，但也增加了我们患神经疾病的易感性。这些特征有些是人类特有的，有些则与相关物种共有，它们在大脑发育的不同阶段表现出来。在这个多阶段的过程中，神经干细胞增殖产生大量多样的祖细胞池，产生兴奋性或抑制性神经元，在进一步成熟过程中整合到回路中。这个过程在不同物种之间跨越不同的时间尺度展开，并且在人类谱系中逐渐变慢，发育节奏的差异与大脑大小、细胞数量和多样性以及连接性的差异相关。在这里，我们引入了“迟滞”和“超速”这两个术语来分别描述发育节奏的减缓和加速。我们回顾了最近跨学科的技术进步，包括体外模型的高级工程、功能比较遗传学和高通量单细胞分析，这些进步正在深入了解人类大脑的特化是如何在迟滞的神经发育过程中产生的。新兴的见解表明，遗传学、基因调控网络、细胞创新和发育节奏起着核心作用，它们共同促成了人类在神经发育的各个阶段和进化的不同点的特化的建立。
