Involvement of rhombomere 4 in the formation of the vestibular system. Studies in Hoxb1 mutants of Mus musculus

The adult brainstem controls vital functions by processing sensory information and motor coordination. During development, the hindbrain, the major part of the adult brainstem, becomes transiently subdivided rostrocaudally into repeated compartments, called rhombomeres (r). We have previously shown that rhombomere 4 (r4) contributes to structurally- and functionally linked sensory afferent and motor efferent components of the central auditory system, and that in the absence of Hoxb1, the main r4 selector gene, mutant mice have severe hearing problems (Di Bonito et al., 2013). Little is known on whether and how r4 participates in the formation of the vestibular system which develops very close to the auditory one. The vestibular nuclear complex consists of a collection of sensory nuclei that integrates and relays information essential for coordination of eye movements, balance, and posture. By using a combination of retrograde labeling and mouse genetics, we could show that r4 fully contributes to the lateral vestibular spinal tract (LVST) that provides input into spinal motoneurons driving extensor muscles of the limb. Labelling in Hoxb1 mutant embryos confirm specific absence of the LVST and of the vestibular efferent neurons (VEN), in accordance with loss of r4 identity and ectopic production of r3 neurons. Mutant pups show some severe defects in the coordination of the lower limbs and seem to lack the vestibulospinal reflex, but adult mice behave normally. Accordingly, TEM Investigations on saccule, utricle maculae and crista ampollaris of Hoxb1 null adults, show presence of bot afferent and efferent endings to sensory cells. This suggests a compensatory mechanism by other neuronal tract supplying the absence of the LVST and the VENs, and more generally it indicates a high degree of plasticity of the vestibular system in rodents.