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Disrupted Brain Progenitor Development and Signaling as a New Mechanism Underlying Microcephaly

GSE279902 Homo sapiens Expression profiling by high throughput sequencing 4 samples Submitted 2025/10/01 Platform GPL24676
Summary
Brain development relies on precise temporal and spatial patterning of progenitors, which form distinct brain regions. Mutations in the NDE1 gene cause severe developmental disorders like microlissencephaly and microhydranencephaly, characterized by abnormal brain morphology. To explore how NDE1 mutations disrupt brain development, we used human-derived models and validated findings in a mouse model. We applied advanced techniques, including microfluidic devices, live imaging, brain organoids, and RNA sequencing, to identify shifts in progenitor identity and extended mitosis duration. The NDE1 knockout altered the rostrocaudal axis, reducing forebrain size and affecting the dorsoventral axis by elevating ventral markers. Mechanistically, abnormal FGF and ERK signaling pathways were implicated. These findings reveal critical insights into the molecular mechanisms driving brain malformations linked to NDE1 mutations, suggesting a novel mechanism for microcephaly.
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Also filed as BioProject PRJNA1175352 and SRA study SRP539662. Searching any of these in the dataset finder brings you back here.

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