人脑的制造仍然是一个大多数神秘的过程，它从胚胎神经管竞争到新生儿大脑中超过1000亿个相互联系的神经元。为了实现这一生物工程的奇迹，在整个怀孕过程中，发育中的胎儿大脑必须平均每分钟增长约25万神经细胞。

These nerve cells are often generated far from where they will eventually reside and function in the new brain, a migration that, while much investigated in animal models using chemical or biological tracers, has never been studied directly in humans. Until now.

在2022年4月20日在线发布的新论文中Nature，加州大学圣地亚哥分校医学院和荷兰儿童基因组医学研究所的科学家描述了通过研究最近从自然原因逝世的健康成年人来推断胎儿发育过程中人类脑细胞运动的新方法。

“Every time a cell divides into two daughter cells, by chance, there arise one or more new mutations, which leave a trail of breadcrumbs that can be read out by modern DNA sequencers,” said senior author Joseph Gleeson, MD, Rady Professor of Neuroscience at UC San Diego School of Medicine and director of neuroscience research at the Rady Children’s Institute for Genomic Medicine.

“By developing methods to read these mutations across the brain, we are able to reveal key insights into how the human brain forms, in comparison with other species.”

尽管人体中有30亿个DNA碱基，并且在人体中有超过30万亿个细胞，但同事将精力集中在仅几百个DNA突变上，这些突变可能在胚胎受精后的前几个细胞分裂中可能出现。大脑。通过在已故个体中跟踪整个大脑中的这些突变，他们能够首次重建人脑的发展。

To understand the type of cells displaying these breadcrumb mutations, they developed methods to isolate each of the major cell types in the brain. For instance, by profiling the mutations in excitatory neurons compared with inhibitory neurons, they confirmed the long-held suspicion that these two cell types are generated in different germinal zones of the brain, and then later mix together in the cerebral cortex, the outermost layer of the organ.

However, they also discovered that the mutations found in the left and right sides of the brain were different from one another, suggesting that — at least in humans — the two cerebral hemispheres separate during development much earlier than previously suspected.

加州大学圣地亚哥加州大学圣地亚哥大学前项目科学家马丁·W·布鲁斯（Martin W.科罗拉多大学医学院。

Breuss is co-first author with Xiaoxu Yang, PhD, postdoctoral scholar and Johannes C. M. Schlachetzki, MD, project scientist, both at UC San Diego; and Danny Antaki, PhD, a former postdoctoral scholar at UC San Diego, now at Twist Biosciences.

作者说：“这项研究解决了为什么这些焦点几乎始终仅限于大脑半球的谜团。将这些结果应用于其他神经系统疾病可以帮助科学家了解更多大脑的奥秘。”

Reference:Breuss MW, Yang X, Schlachetzki JCM, et al. Somatic mosaicism reveals clonal distributions of neocortical development.Nature。2022. doi：10.1038/s41586-022-04602-7

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