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Updated: Apr 14, 2026

Live Imaging of Mitosis in the Developing Mouse Embryonic Cortex
Published on: June 4, 2014
MELK is Required for G2/M Phase Progression in Cortical Progenitors: Insights from Rare ASD-Associated Variants
Liyang Zhao1, Xianjing Li1, Kang Yang1
1National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), NHC Key Laboratory of Mental Health (Peking University), Peking University Sixth Hospital, Peking University Institute of Mental Health, No. 51 Huayuanbei Road, Haidian District, Beijing, 100191, China.
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.
Insights
Maternal embryonic leucine zipper kinase (MELK) is crucial for embryonic brain development. This study reveals MELK regulates neural progenitor cell cycle and neuron formation, linking it to neurodevelopmental conditions like autism spectrum disorder (ASD).
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
Background:
- Maternal embryonic leucine zipper kinase (MELK) is a known cell cycle regulator.
- Its specific function in embryonic cortical development and neurodevelopmental conditions like autism spectrum disorder (ASD) is largely unknown.
Purpose of the Study:
- To investigate the role of MELK in embryonic cortical development.
- To explore the potential mechanistic link between MELK function and neurodevelopmental conditions.
Main Methods:
- Analysis of ultra-rare MELK variants in individuals with ASD.
- In utero electroporation in mouse models to assess Melk knockdown effects.
- Single-cell transcriptomics and FACS-sorted cell analysis to examine gene expression changes.
Main Results:
- MELK expression is enriched in neural progenitors and correlates with the G2/M phase of the cell cycle.
- Melk knockdown in mice impairs progenitor cell cycle progression (G2/M phase) and neuronal migration.
- Downregulation of G2/M phase genes and cytoskeletal regulators involved in neuronal morphogenesis was observed in Melk-knockdown cells.
Conclusions:
- MELK is identified as a critical regulator of G2/M phase progression in neural progenitors during cortical development.
- MELK plays a vital role in neuronal morphogenesis, impacting cell migration and process extension.
- These findings establish a mechanistic link between MELK dysfunction and neurodevelopmental conditions.
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