RhoA in postnatal spinal motoneuron is essential for peripheral myelination

Abstract

Peripheral myelination requires precise axon-glia communication, yet the neuronal intrinsic machinery that governs the release of axonal signals remains incompletely understood. 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 cells differentiation, lipid biosynthesis, and myelin formation. Together, this study reveals a novel, non-cell-autonomous role for RhoA and provides further insights into the complexity of neuronal control over peripheral myelination. This study used motoneuron-specific conditional knockout mice to explore the role of neuronal RhoA in postnatal myelination. Results revealed that neuronal RhoA deficiency down-regulates axonal NRG1-Ⅲ secretion via ROCK2/p-Erk/SP1/BACE1 axis which leads to hypomyelination in peripheral nerve.