Ciliary integrity defines a central canal repair checkpoint linking microtubule stabilization to spinal cord regeneration

Abstract

Microtubule-stabilizing agents consistently improve functional recovery after spinal cord injury (SCI), yet the structural mechanism underlying their shared therapeutic effects remains unclear. Here, we find that chemically distinct stabilizers converge on preservation of ciliary integrity within central canal-associated cells, including ependymal cells and cerebrospinal fluid-contacting neurons. Using complementary SCI models, including complete transection and crush injury, we observe that maintenance of ciliary architecture is associated with reduced glial scarring, improved tissue continuity, and enhanced locomotor recovery. Single-cell transcriptomic analysis further identifies these cell populations as prominent responders to microtubule stabilization, with ciliogenesis-related programs selectively preserved. Importantly, pharmacological disruption of cilia-associated signaling attenuates recovery, whereas promoting ciliogenesis partially recapitulates therapeutic effects, identifying ciliary integrity as a critical cilia-associated structural dependency that contributes to microtubule-stabilizer-mediated spinal cord repair. Together, these findings identify a cilia-dependent central canal regenerative niche as a candidate structural checkpoint linking microtubule stabilization to functional recovery after SCI and identify ciliogenesis as a therapeutically actionable target for SCI. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=151 SRC="FIGDIR/small/733052v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@320578org.highwire.dtl.DTLVardef@5240dorg.highwire.dtl.DTLVardef@181f251org.highwire.dtl.DTLVardef@4bacd1_HPS_FORMAT_FIGEXP M_FIG C_FIG