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<p>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.</p> Graphical Abstract <p></p>

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月13日

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

摘要

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.

Graphical Abstract