MELK is Required for G2/M Phase Progression in Cortical Progenitors: Insights from Rare ASD-Associated Variants.

IF 4.8 4区医学 Q3 CELL BIOLOGY

Cellular and Molecular Neurobiology Pub Date : 2026-04-13 DOI:10.1007/s10571-026-01728-4

Liyang Zhao, Xianjing Li, Kang Yang, Miaomiao Jiang, Zhonghe Chen, Yiqian Shao, Tianlan Lu, Dai Zhang, Lifang Wang, Jun Li

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引用次数: 0

Abstract

Maternal embryonic leucine zipper kinase (MELK) is a cell cycle regulator, yet its role in embryonic cortical development remains unclear. We identified ultra-rare, predicted loss-of-function MELK variants in ASD individuals, prompting this functional investigation. Published human single-cell transcriptomics showed that MELK expression is enriched in neural progenitors and correlates with the G2/M phase. Using in utero electroporation in mouse cortex, we found that Melk knockdown reduced the proportion of progenitors in G2/M phase. Knockdown also caused impaired multipolar-to-bipolar transition and shorter leading processes. Complementing these findings, transcriptomic analysis of FACS-sorted Melk-knockdown cortical cells revealed downregulation of G2/M-related genes and cytoskeletal regulators linked to neuronal morphogenesis. Together, these findings identify MELK as a critical regulator of both G2/M phase progression and neuronal morphogenesis during cortical development, providing a mechanistic link to neurodevelopmental conditions.

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MELK是皮质祖细胞G2/M期进展所必需的：来自罕见asd相关变异的见解

母胚亮氨酸拉链激酶（MELK）是一种细胞周期调节因子，但其在胚胎皮质发育中的作用尚不清楚。我们在ASD个体中发现了超罕见的，可预测的功能丧失MELK变异，从而促进了这项功能研究。已发表的人类单细胞转录组学表明，MELK在神经祖细胞中表达丰富，并与G2/M期相关。通过对小鼠皮层的子宫电穿孔实验，我们发现Melk基因敲除降低了G2/M期祖细胞的比例。击倒也会导致多极到双极的转变受损，导致前导过程缩短。与这些发现相补充的是，facs分类的melk敲除皮质细胞的转录组学分析显示，G2/ m相关基因和与神经元形态发生相关的细胞骨架调节因子下调。总之，这些发现确定了MELK是皮质发育过程中G2/M期进展和神经元形态发生的关键调节因子，提供了与神经发育状况的机制联系。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cellular and Molecular Neurobiology 生物-神经科学

CiteScore

7.70

自引率

0.00%

发文量

137

审稿时长

4-8 weeks

期刊介绍： Cellular and Molecular Neurobiology publishes original research concerned with the analysis of neuronal and brain function at the cellular and subcellular levels. The journal offers timely, peer-reviewed articles that describe anatomic, genetic, physiologic, pharmacologic, and biochemical approaches to the study of neuronal function and the analysis of elementary mechanisms. Studies are presented on isolated mammalian tissues and intact animals, with investigations aimed at the molecular mechanisms or neuronal responses at the level of single cells. Cellular and Molecular Neurobiology also presents studies of the effects of neurons on other organ systems, such as analysis of the electrical or biochemical response to neurotransmitters or neurohormones on smooth muscle or gland cells.