大脑皮层发育中的神经元生长锥的动态亚型和上下文特异性亚细胞RNA调控，这一成果由哈佛大学Jeffrey D. Macklis团队经过不懈努力而取得。相关论文于2025年12月29日发表于国际顶尖学术期刊《自然—神经科学》杂志上。

在这里，该课题组人员研究了发育中的大脑皮层远程投射神经元（PNs）生长轴突尖端的亚型特异性生长锥（GCs）内信使RNA的定位和稳定性。通过比较两种PNs亚型（半球间胼胝体和皮质丘脑）在不同发育阶段的GC定位转录组，发现了不同和共享的亚细胞机制，这些机制涉及不同的生长阶段、靶神经支配和突触发生，以及与神经发育和神经精神疾病相关的基因富集。此外，研究团队研究了动态GC定位mRNAs的序列元件，在3'非翻译区域鉴定了gc富集的基序。例如，研究团队发现翻译调节因子CPEB4调节轴突分支，RBMS1在胼胝体回路形成中动态起作用。这项工作为其他极化细胞的亚细胞特化提供了概括性的见解，有助于阐明神经发育和行为认知障碍。

研究人员表示，不同亚型的神经元通过不同的定位和翻译特异性RNA来划分亚型特异性功能，但潜在的机制尚不清楚。

附：英文原文

Title: Dynamic subtype- and context-specific subcellular RNA regulation in growth cones of developing neurons of the cerebral cortex

Author: Veeraraghavan, Priya, Engmann, Anne K., Hatch, John J., Itoh, Yasuhiro, Nguyen, Duane, Addison, Thomas, Macklis, Jeffrey D.

Issue&Volume: 2025-12-29

Abstract: Neurons of distinct subtypes compartmentalize subtype-specific function in part by differentially localizing and translating specific RNAs, but underlying mechanisms are not understood. Here we investigate messenger RNA localization and stability within subtype-specific growth cones (GCs), leading tips of growing axons, of long-range projection neurons (PNs) of the developing cerebral cortex. Comparison of GC-localized transcriptomes between two subtypes of PNs (interhemispheric-callosal and corticothalamic) across developmental stages identified both distinct and shared subcellular machinery involved in distinct phases of growth, target innervation and synaptogenesis, and enrichment of genes associated with neurodevelopmental and neuropsychiatric disorders. Further, we investigated sequence elements in dynamically GC-localized mRNAs, identifying GC-enriched motifs in 3′ untranslated regions. For example, we identified that CPEB4, a translational regulator, regulates axonal branching and that RBMS1 functions dynamically in callosal circuit formation. This work offers generalizable insights for subcellular specialization in other polarized cells, toward elucidating neurodevelopmental and behavioral-cognitive disorders.

DOI: 10.1038/s41593-025-02173-0

Source: https://www.nature.com/articles/s41593-025-02173-0