在大脑皮层发育过程中，人类基底放射神经胶质细胞（bRGCs）具有高度的自我更新和神经发生能力。对该细胞类型的选择压可能促使人类新皮质的进化，从而导致皮层大小的增加。bRGCs具有富集的Forkhead Box P1（FOXP1）表达，这是一种与自闭症谱系障碍等神经发育障碍（NDDs）相关的转录因子。然而，在皮质发育过程中FOXP1在bRGCs中的细胞特异性作用尚未被探索。在这里，我们使用人类脑器官生成体来研究FOXP1基因表达调控在产生bRGCs过程中的需求。我们在FOXP1表达在皮层祖细胞中最高、bRGCs开始积极产生神经元时的发育时间点进行检查。通过失去FOXP1，我们显示bRGCs的数量减少，剩余bRGCs的增殖和分化也减少，这些都导致兴奋性皮层神经元数量的减少。通过使用单核RNA测序和细胞轨迹分析，我们揭示了FOXP1在调节与神经发生和NDDs相关的关键信号通路时对皮层祖细胞增殖和分化的作用。总之，这些结果表明FOXP1在早期皮层发育中调控了人类特定特征。版权：© 2023 Park et al. 这是一篇以创作共用许可证（CC BY）方式发布的开放获取文章，根据该许可证，任何人都可以自由使用、分发和再现本文，只要保留原文作者和来源的信息。

During cortical development, human basal radial glial cells (bRGCs) are highly capable of sustained self-renewal and neurogenesis. Selective pressures on this cell type may have contributed to the evolution of the human neocortex, leading to an increase in cortical size. bRGCs have enriched expression for Forkhead Box P1 (FOXP1), a transcription factor implicated in neurodevelopmental disorders (NDDs) such as autism spectrum disorder. However, the cell type-specific roles of FOXP1 in bRGCs during cortical development remain unexplored. Here, we examine the requirement for FOXP1 gene expression regulation underlying the production of bRGCs using human brain organoids. We examine a developmental time point when FOXP1 expression is highest in the cortical progenitors, and the bRGCs, in particular, begin to actively produce neurons. With the loss of FOXP1, we show a reduction in the number of bRGCs, as well as reduced proliferation and differentiation of the remaining bRGCs, all of which lead to reduced numbers of excitatory cortical neurons over time. Using single-nuclei RNA sequencing and cell trajectory analysis, we uncover a role for FOXP1 in directing cortical progenitor proliferation and differentiation by regulating key signaling pathways related to neurogenesis and NDDs. Together, these results demonstrate that FOXP1 regulates human-specific features in early cortical development.Copyright: © 2023 Park et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.