| First Author | Cantu-Guerra HL | Year | 2023 |
| Journal | Dev Dyn | Volume | 252 |
| Issue | 1 | Pages | 124-144 |
| PubMed ID | 36284453 | Mgi Jnum | J:332313 |
| Mgi Id | MGI:7414397 | Doi | 10.1002/dvdy.548 |
| Citation | Cantu-Guerra HL, et al. (2023) Cochlear hair cell innervation is dependent on a modulatory function of Semaphorin-3A. Dev Dyn 252(1):124-144 |
| abstractText | BACKGROUND: Proper connectivity between type I spiral ganglion neurons (SGNs) and inner hair cells (IHCs) in the cochlea is necessary for conveying sound information to the brain in mammals. Previous studies have shown that type I SGNs are heterogeneous in form, function and synaptic location on IHCs, but factors controlling their patterns of connectivity are not well understood. RESULTS: During development, cochlear supporting cells and SGNs express Semaphorin-3A (SEMA3A), a known axon guidance factor. Mice homozygous for a point mutation that attenuates normal SEMA3A repulsive activity (Sema3a(K108N) ) show cochleae with grossly normal patterns of IHC innervation. However, genetic sparse labeling and three-dimensional reconstructions of individual SGNs show that cochleae from Sema3a(K108N) mice lacked the normal synaptic distribution of type I SGNs. Additionally, Sema3a(K108N) cochleae show a disrupted distribution of GLUA2 postsynaptic patches around the IHCs. The addition of SEMA3A-Fc to postnatal cochleae led to increases in SGN branching, similar to the effects of inhibiting glutamate receptors. Ca(2+) imaging studies show that SEMA3A-Fc decreases SGN activity. CONCLUSIONS: Contrary to the canonical view of SEMA3A as a guidance ligand, our results suggest SEMA3A may regulate SGN excitability in the cochlea, which may influence the morphology and synaptic arrangement of type I SGNs. |
