近日，美国密歇根大学教授E. Josephine Clowney及其团队的最新研究揭示了转录因子编码大脑的神经元基底图。相关论文于2026年5月27日发表在《自然》杂志上。

在这里，研究人员开发了一种方法，在黑腹果蝇中嵌入经过充分研究的神经元，这些神经元在产生它们的神经元谱系的转录环境中调节交配。通过比较谱系内和谱系之间的转录，研究小组发现了大量以复杂组合表达的转录因子，这些转录因子描绘了大脑半谱系——有丝分裂后神经元的类别，来自同一干细胞，共享Notch状态。半谱系包括大脑中的主要解剖类别，这些转录因子需要产生它们的总体特征。

研究小组发现，相同半谱系的亚型可以为调节不同驱动的电路提供一个共同的计算模块，并确定了一组正交的转录因子，这些转录因子可以对不同出生顺序的半谱系亚型进行分层。他们的发现表明，不同的转录因子组在一个等级系统中运作，以建立、多样化和性别区分构成动机行为回路的线性相关神经元。通过将发育模式与产生信息流的粗细方面的可分离转录轴联系起来，研究团队为大脑控制各种驱动提供了一个逻辑框架。

据悉，调节动机行为的大脑区域，包括脊椎动物的下丘脑和节肢动物的大脑，都有专门用于感知和内部调节许多行为状态的神经回路。这些电路是由复杂的细胞类型组成的，其模式一直难以阐明。

附：英文原文

Title: Transcription factor codes patterning neuronal groundplans of the cerebrum

Author: Elkahlah, Najia A., Lin, Yunzhi, Pan, Yijie, Carter, Joseph A., Shirangi, Troy R., Josephine Clowney, E.

Issue&Volume: 2026-05-27

Abstract: Brain regions that regulate motivated behaviours, including the vertebrate hypothalamus and arthropod cerebrum, house bespoke neural circuits dedicated to perceptual and internal regulation of many behavioural states1,2. These circuits are built to purpose from complex sets of cell types whose patterning has been challenging to elucidate. Here we developed methods in Drosophila melanogaster to embed well-studied neurons that regulate mating in the transcriptional contexts of the neuronal lineages that generate them3,4,5. By comparing transcription within and between lineages, we identified a large set of transcription factors expressed in complex combinations that delineate cerebral hemilineages—classes of postmitotic neurons born from the same stem cell and sharing Notch status6,7. Hemilineages comprise the major anatomic classes in the cerebrum8,9,10 and these transcription factors are required to generate their gross features. We show that subtypes of the same hemilineage can provide a common computational module to circuits regulating different drives, and identify an orthogonal set of transcription factors that stratify hemilineage subtypes of differing birth order. Our findings suggest that distinct sets of transcription factors operate in a hierarchical system to build, diversify and sexually differentiate lineally related neurons that compose motivated behaviour circuits. By linking developmental patterning to separable transcriptional axes that produce gross versus fine aspects of information flow, we provide a logical framework for cerebral control of diverse drives.

DOI: 10.1038/s41586-026-10526-3

Source: https://www.nature.com/articles/s41586-026-10526-3