Ddx3x deficiency in mice impairs corticofugal motor circuits and causes motor deficits that are attenuated by early-life exercise.

Ddx3x haploinsufficiency in mice impairs corticopontine motor circuits and adult motor performance, with benefits in haploinsufficient females that are attenuated by early-life exercise.

• Why it matters: DDX3X variants are linked to pervasive, often severe motor problems, but the circuit mechanisms and whether early intervention can improve motor trajectories are unclear.
• What they did: Using mouse models, the study mapped corticofugal motor circuitry, tested dendritic arborization in corticopontine neurons, induced juvenile-onset Ddx3x loss, and compared motor outcomes with chemogenetic circuit disruption and juvenile motor intervention.
• The result: Ddx3x regulates corticopontine neuron development and later plasticity; juvenile-onset loss reproduces adult motor impairments, and juvenile motor intervention yields long-lasting, sex-dependent improvements in adult motor function.

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