抑制型间神经元调控皮层回路活动，它们的功能失调涉及到自闭症谱系障碍（ASD）。16p11.2微缺失与ASD案例的1％存在遗传联系。然而，很少有研究探讨这种微缺失对间神经元发育的影响。利用人诱导多能干细胞来源的腹侧大脑器官小体，我们研究了这种微缺失对小体大小、祖细胞增殖以及组织形成到神经玫瑰花环，早期发育时间点的节后期标记表达以及后期神经元标记NEUN表达的影响。在早期阶段，缺失小体在大小上呈现更大的变化，同时相对神经玫瑰花环面积和腹侧大脑标记COUPTFII表达增加，这些属性的变异性增加。细胞周期分析显示，总细胞周期长度增加主要由于G1期延长，其持续时间也比正常情况更加变异。在后期阶段，缺失小体增加了NEUN表达。我们认为16p11.2微缺失增加了发育的变异性，可能通过延长腹侧祖细胞的细胞周期，促进过早分化成间神经元，从而促进ASD的发病。©2023年。由生物学家有限公司出版。

Inhibitory interneurons regulate cortical circuit activity, and their dysfunction has been implicated in autism spectrum disorder (ASD). 16p11.2 microdeletions are genetically linked to 1% of ASD cases. However, few studies investigate the effects of this microdeletion on interneuron development. Using ventral telencephalic organoids derived from human induced pluripotent stem cells, we have investigated the effect of this microdeletion on organoid size, progenitor proliferation and organisation into neural rosettes, ganglionic eminence marker expression at early developmental timepoints, and expression of the neuronal marker NEUN at later stages. At early stages, deletion organoids exhibited greater variations in size with concomitant increases in relative neural rosette area and the expression of the ventral telencephalic marker COUPTFII, with increased variability in these properties. Cell cycle analysis revealed an increase in total cell cycle length caused primarily by an elongated G1 phase, the duration of which also varied more than normal. At later stages, deletion organoids increased their NEUN expression. We propose that 16p11.2 microdeletions increase developmental variability and may contribute to ASD aetiology by lengthening the cell cycle of ventral progenitors, promoting premature differentiation into interneurons.© 2023. Published by The Company of Biologists Ltd.