RhoA in postnatal spinal motoneuron is essential for peripheral myelination

Here, we discover that RhoA, a classic cytoskeletal regulator, is highly expressed in postnatal spinal motoneurons and unexpectedly governs this axon-glia communication. RhoA conditional knockout in postnatal motoneurons causes profound peripheral hypomyelination without affecting neuronal survival, dendrites, or axonal caliber.

Mechanistically, RhoA deficiency in postnatal spinal motoneurons attenuates ROCK2/p-Erk/SP1/BACE1 signaling and NRG1-III secretion, then disrupts Schwann cell’s differentiation, lipid biosynthesis, and myelin formation. Together, this study reveals a novel, non-cell-autonomous role for RhoA, and provides new insights into the complexity of neuronal control over peripheral myelination.