德国马克斯·普朗克分子细胞生物学和遗传学研究所Wieland B. Huttner课题组的研究表明，人类TKTL1提示现代人的额叶新皮层比尼安德特人有更强的神经生成能力。该研究于2022年9月9日发表于国际一流学术期刊《科学》。

尼安德特人的大脑与现代人的大脑大小相似。研究人员试图揭示在新皮层发育过程中神经发生的潜在差异。现代人的转酮醇酶样1（TKTL1）与尼安德特人的TKTL1不同，它有一个赖氨酸-精氨酸的氨基酸替换。利用在发育中的小鼠和雪貂新皮层中的过表达，在胎儿人类新皮层组织中的敲除，以及基因组编辑的大脑类器官，研究人员发现现代人的变体hTKTL1，而不是尼安德特人的变体，增加了基底放射状胶质细胞（bRG）的丰度，而非中间祖细胞（bIP）。

hTKTL1的作用需要磷酸戊糖途径和脂肪酸的合成。抑制这些代谢途径会降低胎儿人类新皮层组织中bRG的丰度。这些数据表明，现代人的新皮层神经发生不同于尼安德特人。

附：英文原文

Title: Human TKTL1 implies greater neurogenesis in frontal neocortex of modern humans than Neanderthals

Author: Anneline Pinson, Lei Xing, Takashi Namba, Nereo Kalebic, Jula Peters, Christina Eugster Oegema, Sofia Traikov, Katrin Reppe, Stephan Riesenberg, Tomislav Maricic, Razvan Derihaci, Pauline Wimberger, Svante Pbo, Wieland B. Huttner

Issue&Volume: 2022-09-09

Abstract: Neanderthal brains were similar in size to those of modern humans. We sought to investigate potential differences in neurogenesis during neocortex development. Modern human transketolase-like 1 (TKTL1) differs from Neanderthal TKTL1 by a lysine-to-arginine amino acid substitution. Using overexpression in developing mouse and ferret neocortex, knockout in fetal human neocortical tissue, and genome-edited cerebral organoids, we found that the modern human variant, hTKTL1, but not the Neanderthal variant, increases the abundance of basal radial glia (bRG) but not that of intermediate progenitors (bIPs). bRG generate more neocortical neurons than bIPs. The hTKTL1 effect requires the pentose phosphate pathway and fatty acid synthesis. Inhibition of these metabolic pathways reduces bRG abundance in fetal human neocortical tissue. Our data suggest that neocortical neurogenesis in modern humans differs from that in Neanderthals.

DOI: abl6422

Source: https://www.science.org/doi/10.1126/science.abl6422