Evolution and Development of the Inner Ear Efferent System: Transforming a Motor Neuron Population to Connect to the Most Unusual Motor Protein via Ancient Nicotinic Receptors

Abstract

All craniate chordates have inner ears with hair cells that receive input from the brain by cholinergic centrifugal fibers, the so-called inner ear efferents (IEEs). Comparative data suggest that IEEs derive from facial branchial motor (FBM) neurons that project to the inner ear instead of facial muscles. Developmental data showed that IEEs develop adjacent to FBMs and segregation from IEEs might depend on few transcription factors uniquely associated with IEEs. Like other cholinergic terminals in the peripheral nervous system (PNS), efferent terminals signal on hair cells through nicotinic acetylcholine channels, likely composed out of alpha 9 and alpha 10 units (Chrna9, Chrna10). Consistent with the evolutionary ancestry of IEEs is the even more conserved ancestry of Chrna9 and 10. The evolutionary appearance of IEEs may reflect access of FBMs to a novel target, possibly related to displacement or loss of mesoderm-derived muscle fibers by the ectoderm-derived ear vesicle. Experimental transplantations mimicking this possible aspect of ear evolution showed that different motor neurons of the spinal cord or brainstem form cholinergic synapses on hair cells when ears replace somites or eyes. Transplantation provides experimental evidence in support of the evolutionary switch of FBM neurons to become IEEs. Mammals uniquely evolved a prestin related motor system to cause shape changes in outer hair cells regulated by the IEEs. In summary, an ancient motor neuron population drives in craniates via signaling through highly conserved Chrna receptors a uniquely derived cellular contractility system that is essential for hearing in mammals.

Ear transplantations reveal conservation of inner ear afferent pathfinding cues

“…Transplantation of an ear adjacent to trigeminal branchial motor neurons are additional support that any motor neuron can become an efferent to the ear, should the ear be placed in their axonal trajectory. This further supports the hypothesis that inner ear efferents arose from rerouted facial branchial motor neurons when the ear evolved in ancestral craniates in the place of somite-derived muscle tissue 37 , 53 , 54 .…”

Sonic hedgehog antagonists reduce size and alter patterning of the frog inner ear

“…(C)]. While muscle fibers are thus adjacent to hair cells and could possibly receive inner ear efferents as demonstrated for other motor neurons projecting to ears (Elliott et al, ; Fritzsch and Elliott, ) we could trace all innervation to postotic efferents, suggesting the anterior translocation of muscle fibers is accompanied by translocating the innervation instead of receiving new innervation from inner ear efferents of facial branchial motoneurons.…”

Development and Functional Organization of the Cranial Nerves in Lampreys

“…E). These centrifugal cells were reported to be cholinergic in lampreys (Pombal et al, ), which is similar to the situation in other vertebrates (reviewed in Fritzsch and Elliott, ). Additionally, in this review on the evolution and development of the inner ear efferent system in craniates, the authors suggest that inner ear efferents derive from facial branchial motoneurons, which project to the inner ear instead of facial muscles (Fritzsch and Elliott, ).…”