美国康涅狄格大学医学院James Y. H. Li小组的研究发现FOXP基因调控浦肯野细胞多样性和小脑形态发生。相关论文于2025年8月18日发表于国际顶尖学术期刊《自然—神经科学》杂志上。

利用单细胞RNA测序，课题组在胚胎母位小脑中鉴定出至少11种分子上不同的PC亚型。空间重建显示，这些亚型以胚胎模式组织，预测成人小脑结构的关键特征，包括纵向条纹和小叶特异性。PC亚型身份由Foxp1、Foxp2和Foxp4的组合表达来定义。Foxp1和Foxp2的基因缺失会破坏PC多样化和小脑模式，包括Foxp1⁺亚型的缺失和小脑半球形成的失败。Foxp1⁺ PCs在胎儿人类小脑中富集，但在小鸡中很少见，这表明Foxp1⁺ PCs在小脑进化中起作用。这些发现揭示了早期PC多样化，并确定Foxp1+ PC是小脑半球发育的关键调节因子。

研究人员表示，小脑浦肯野细胞（PCs）是小脑皮层唯一的输出神经元，对运动协调、学习和电路形成至关重要。虽然功能多样，但PC异质性的程度和这种多样性的分子驱动因素仍不清楚。

附：英文原文

Title: FOXP genes regulate Purkinje cell diversity and cerebellar morphogenesis

Author: Khouri-Farah, Nagham, Guo, Qiuxia, Perry, Thomas A., Dussault, Ryan, Li, James Y. H.

Issue&Volume: 2025-08-18

Abstract: Cerebellar Purkinje cells (PCs), the sole output neurons of the cerebellar cortex, are essential for motor coordination, learning and circuit formation. While functionally diverse, the extent of PC heterogeneity and the molecular drivers of this diversity remain unclear. Using single-cell RNA sequencing, we identified at least 11 molecularly distinct PC subtypes in the embryonic mouse cerebellum. Spatial reconstruction revealed that these subtypes are organized in embryonic patterns that predict key features of adult cerebellar architecture, including longitudinal stripes and lobular specificities. PC-subtype identity is defined by the combinatorial expression of Foxp1, Foxp2 and Foxp4. Genetic deletion of Foxp1 and Foxp2 disrupts PC diversification and cerebellar patterning, including the loss of a Foxp1+ subtype and the failure of cerebellar hemisphere formation. Foxp1+ PCs are enriched in the fetal human cerebellum but are rare in chick, suggesting a role in cerebellar evolution. These findings uncover early PC diversification and identify Foxp1+ PCs as critical regulators of cerebellar hemispheric development.

DOI: 10.1038/s41593-025-02042-w

Source: https://www.nature.com/articles/s41593-025-02042-w