Defective neuronal differentiation in Lowe syndrome is associated with mitochondrial dysfunction and impaired cilia-related Sonic Hedgehog signaling.

OCRL deficiency in Lowe syndrome causes mitochondrial dysfunction, impaired cilia-related Sonic Hedgehog signaling, and disrupted neuronal differentiation across multiple models.

• Why it matters: Understanding the cellular mechanisms behind neurodevelopmental delays in Lowe syndrome is crucial, as the disorder involves complex metabolic and signaling pathway disruptions that are not yet fully elucidated.
• What they did: Researchers used patient-derived iPSC neurons, an Ocrl knockout mouse, and zebrafish models to investigate OCRL loss, revealing conserved mitochondrial defects, altered neural differentiation, and impaired Hedgehog signaling.
• The result: Findings demonstrate that OCRL deficiency leads to reduced mitochondrial activity, increased oxidative stress, and disrupted neural lineage balance, providing insights into the interconnected pathways underlying Lowe syndrome pathology.