A filopodia-based dendritic mechanosensory compartment in CSF-contacting neurons

Cerebrospinal fluid-contacting neurons (CSF-cNs) are spinal sensory cells that detect chemical and mechanical stimuli via PKD2L1 channels located on a primary cilium, as established in aquatic vertebrates like zebrafish. The mechanosensory mechanism in mammals, however, has remained unclear due to the absence of definitive evidence for cilia on their apical processes (ApPrs). Here we show that mouse CSF-cN ApPrs lack cilia but instead possess drebrin-stabilized filopodia enriched with F-actin. Mechanical stimulation of these cilia-free ApPrs elicits robust, PKD2L1-dependent inward currents, that are sufficient to drive neuronal firing, confirming a novel, cilia-independent mechanosensory mechanism. Comparative analyses indicate an evolutionary divergence from ciliary mechanotransduction, with mice adopting a direct, actin-associated mechanism. These findings advance our understanding of the cellular basis of spinal mechanosensation in mammals and reveal a specialized adaptation for monitoring central canal dynamics, with implications for spinal sensory integration and evolution. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/713694v1_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@f74408org.highwire.dtl.DTLVardef@193866forg.highwire.dtl.DTLVardef@5f1baaorg.highwire.dtl.DTLVardef@113c3e_HPS_FORMAT_FIGEXP M_FIG C_FIG In BriefCerebrospinal fluid-contacting neurons detect mechanical forces in the spinal cord. In zebrafish, they use a cane-like cilium. Whether mammals inherited this mechanism is controversial. Here, researchers show that mice have replaced the cilium with filopodia, hair-like, touch-sensitive projections stabilized by the protein drebrin. This evolutionary innovation reveals how sensory cells adapt their machinery to the demands of different body plans and environments. HIGHLIGHTS- Mouse spinal CSF-cN apical processes lack cilia. - Drebrin-stabilized filopodia replace the ancestral cilium. - Direct mechanical stimulation of ApPrs evokes PKD2L1-dependent currents and firing. - Mammalian CSF-cNs evolved a cilia-independent mechanosensory mechanism.