丘脑NRXN 1介导的输入驱动人类皮层祖细胞兴奋性神经发生

丘脑NRXN1介导的输入驱动人类皮层祖细胞兴奋性神经发生

作者： 小柯机器人 发布时间：2026/9/5 17:35:06

本期文章：《科学》：Volume 393 Issue 6815

2026年9月3日，美国加利福尼亚大学Claudia V. Nguyen等科学家在《科学》（Science）发表研究，通过皮层-丘脑类器官融合模型，揭示了丘脑NRXN1介导的输入促进人类皮层兴奋性神经元生成的机制。

人类大脑皮层的发育通过来自皮层内部及其他脑区（包括丘脑）的协调信号进行。然而，丘脑神经元投射如何影响早期人类皮层发育仍不甚清楚。在这项研究中，研究人员通过融合皮层和丘脑类器官来探究丘脑输入如何塑造人类皮层细胞的成熟。利用单核RNA测序和细胞成像，他们发现丘脑输入增加了皮层兴奋性神经元的产生。他们鉴定出neurexin-1（NRXN1）是丘脑轴突与皮层外层放射状胶质细胞之间物理接触的介导因子。丘脑NRXN1的基因敲除减少了这些接触，并减弱了上层兴奋性神经元的产生。这些发现揭示了丘脑输入调控人类皮层祖细胞并塑造发育过程中兴奋性神经元产生的一种机制。

附：英文原文

Title: Thalamic NRXN1-mediated input to human cortical progenitors drives excitatory neurogenesis

Author: Claudia V. Nguyen, Antoni Martija, Daniel C. Jaklic, Rista White, Marty G. Yang, Patricia R. Nano, Jose A. Soto, Jessenya Mil, Dakshesh Rana, Jacqueline M. Martin, Hunter E. Schweiger, Sebastian Hernandez, Elisa Fazzari, Yu Liu, Jack M. Parent, Mohammed A. Mostajo-Radji, Daniel H. Geschwind, Aparna Bhaduri

Issue&Volume: 2026-09-03

Abstract: The human cerebral cortex develops through coordinated signals from within the cortex and from other brain regions, including the thalamus. However, how thalamic neuronal projections influence early human cortical development remains less well-understood. In this study, we fused cortical and thalamic organoids to investigate how thalamic input shapes the maturation of human cortical cells. Using single-nuclei RNA-sequencing and cellular imaging, we found that thalamic input increases the production of cortical excitatory neurons. We identify neurexin-1 (NRXN1) as a mediator of physical contact between thalamic axons and cortical outer radial glia. Genetic knockout of thalamic NRXN1 reduced these contacts and attenuated the production of upper-layer excitatory neurons. These findings reveal a mechanism by which thalamic input regulates human cortical progenitors and shapes excitatory neuron production during development.

DOI: 10.1126/science.ady5180

Source: https://www.science.org/doi/10.1126/science.ady5180

主题：丘脑NRXN1介导