近日，英国MRC分子生物学实验室Erika Donà及其团队研究出果蝇出生顺序和神经元身份的全局分子密码。2026年7月22日出版的《自然》发表了这项成果。

在这里，研究团队展示了黑腹果蝇神经索的高分辨率发育转录图谱，神经索是感觉-运动回路的中心枢纽。与参考连接组相比，它们的图谱具有相当大的38倍的总覆盖率，它们捕获了广泛的分子多样性，并使它们能够与成人连接组进行比较。课题组确定了神经索中神经元多样性的三个发育原则。

首先，神经发生的时间决定了分子身份的多样化：胚胎出生的神经元比幼虫出生的神经元分化得更快，这在成人的连接组中也观察到了。其次，来自所有谱系的神经元共有的17个转录因子为出生顺序提供了一个全局的分子身份编码。最后，通过将性别特异性转录谱映射到连接组，研究小组确定了女性特异性凋亡和转录分化是性别规范的关键全球驱动因素。通过揭示分子身份的关键组织轴，该图谱开辟了剖析支撑神经回路发展和进化的分子机制的途径。

据介绍，功能神经回路的组装依赖于具有精确分子身份和连通性的不同神经类型的产生。解开神经元规格和神经系统连接的一般原理需要对其多样性进行系统和高分辨率的表征，最近单细胞转录组学和连接组学的进展使其成为可能。然而，将神经元的分子特征与电路结构联系起来仍然是一个关键的挑战。

附：英文原文

Title: A global molecular code for birth order and neuronal identity in Drosophila

Author: Cachero, Sebastian, Mitletton, Myrto, Beckett, Isabella R., Marin, Elizabeth C., Capdevila, Laia Serratosa, Gkantia, Marina, Soffers, Jelly H. M., Lacin, Haluk, Jefferis, Gregory S. X. E., Don, Erika

Issue&Volume: 2026-07-22

Abstract: The assembly of functional neural circuits relies on the generation of diverse neural types with precise molecular identity and connectivity. Unlocking general principles of neuronal specification and wiring across the nervous system requires a systematic and high-resolution characterization of its diversity, recently enabled by advances in single-cell transcriptomics and connectomics. However, linking the molecular identity of neurons to circuit architecture remains a key challenge. Here we present a high-resolution developmental transcriptional atlas for the Drosophila melanogaster nerve cord, the central hub for sensory–motor circuits. With a considerable 38× aggregate coverage relative to its reference connectome1,2, our atlas captures extensive molecular diversity and enables robust alignment to the adult connectome. We identified three developmental principles underlying neuronal diversity in the nerve cord. First, the timing of neurogenesis shapes diversification of molecular identity: embryonic-born neurons diverge faster than larval-born neurons, as also observed in the adult connectome. Second, 17 transcription factors common to neurons from all lineages provide a global molecular identity code for birth order. Lastly, by mapping sex-specific transcriptional profiles to the connectome, we identified female-specific apoptosis and transcriptional divergence as key global drivers of sex specification. By revealing key organizational axes of molecular identity, this atlas opens avenues to dissect the molecular mechanisms underpinning the development and evolution of neural circuits.

DOI: 10.1038/s41586-026-10797-w

Source: https://www.nature.com/articles/s41586-026-10797-w