加州大学Alex A. Pollen研究小组在研究中取得进展。他们揭示了哺乳动物纹状体中间神经元的保存与改变。该研究于2025年11月5日发表于国际一流学术期刊《自然》杂志上。

在这里，研究组研究了10种哺乳动物的抑制性神经元的基因表达，跨越160从灵长类动物进化而来的一百万年。课题组人员发现，在发育过程中指定的新生TAC3中间神经元的初始类别代表了祖先的，内侧神经节隆起（MGE）衍生的纹状体群体，也存在于猪和雪貂皮层中。这一发现促使人们重新检查Glires，包括小鼠，它们被认为缺乏TAC3型。在小鼠中靶向富集MGE前体揭示了TAC3初始类的保护，被Tac2 （TAC3的母基同源物）的表达减少和Th的表达增加所掩盖。将他们的分析扩展到成年纹状体，进一步支持了灵长类动物TAC3与无母体纹状体中间神经元的同源性，并在无母体腹内侧纹状体中发现了罕见的Tac2亚群。该研究表明，端脑抑制神经元的初始类别在很大程度上是保守的，并且在进化过程中，哺乳动物大脑中的神经元类型通过再分配和命运改良而改变，而不是通过在发育早期衍生出新的前体。

据悉，哺乳动物的大脑在大小、结构和功能上各不相同，但进化上新的细胞类型在多大程度上促成了这种差异仍未得到解决。先前的研究表明，纹状体抑制性中间神经元存在一种灵长类动物特有的群体——TAC3中间神经元。然而，需要更广泛的分类学和发育特征来解决细胞型进化中的新颖性。

附：英文原文

Title: Conservation and alteration of mammalian striatal interneurons

Author: Corrigan, Emily K., DeBerardine, Michael, Poddar, Aunoy, Turrero Garca, Miguel, de la O, Sean, He, Siting, Sen, Harsha, Duhne, Mariana, Lindberg, Shanti, Song, Menygi, Schmitz, Matthew T., Sears, Karen E., Mallarino, Ricardo, Berke, Joshua D., Harwell, Corey C., Paredes, Mercedes F., Krienen, Fenna M., Pollen, Alex A.

Issue&Volume: 2025-11-05

Abstract: Mammalian brains vary in size, structure and function, but the extent to which evolutionarily novel cell types contribute to this variation remains unresolved1,2,3,4. Previous studies suggest that there is a primate-specific population of striatal inhibitory interneurons—the TAC3 interneurons5. However, broader taxonomic and developmental characterization is required to address novelty in cell-type evolution. Here we examine gene expression in inhibitory neurons across 10 mammalian species, spanning 160million years of divergence from primates. We find that the initial class of newborn TAC3 interneurons specified during development represents an ancestral, medial ganglionic eminence (MGE)-derived striatal population that is also present in pig and ferret cortex. This discovery prompted a re-examination of Glires, including mice, which are thought to lack the TAC3 type5,6. Targeted enrichment of MGE precursors in mice revealed conservation of the TAC3 initial class, camouflaged by reduced expression of Tac2 (the mouse orthologue of TAC3) and a gain of Th expression. Extending our analysis to the adult striatum further supported the homology of primate TAC3 and mouse Th striatal interneurons, and also uncovered a rare Tac2 subpopulation in the mouse ventromedial striatum. This study suggests that initial classes of telencephalic inhibitory neurons are largely conserved, and that during evolution, neuronal types in the mammalian brain change through redistribution and fate refinement, rather than by derivation of novel precursors early in development.

DOI: 10.1038/s41586-025-09592-w

Source: https://www.nature.com/articles/s41586-025-09592-w