HOXB1 AND HOXB2 ARE INVOLVED IN THE DETERMINATION OF THE RHOMBOMERE 4-DERIVED VESTIBULAR SISTEM

The central auditory pathway consists of sensory nuclei that transmit the ascending acoustic information, and efferent motor neurons that modulate primary afferent responses. 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 mutant mice have severe hearing problems. We subsequently demonstrated that Hoxb2 and Hoxa2 and their genetic interactions are also necessary for the proper development of r4. The vestibular nuclear complex, in part derives from r4 and consists of a collection of sensory nuclei that integrates and relays information for the coordination of eye movements, balance and posture. We still used Hoxb1 mutant mice to investigate the contribution of r4 in the developmental patterning of vestibular projection neurons, with particular focus on the lateral vestibulo spinal tract (LVST). Retrograde labelling and marker analysis on Hoxb1 mutant embryos and postnatal pups confirmed 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. However, transmission electron microscopy experiments in adult mice show the presence of both afferent and efferent nervous endings. It is thus plausible that in the adult mouse mutant a compensatory mechanism overtaken by other neuronal tracts is able to compensate for the early absence of the vestibular nuclei, in line with a partial rescue of the vestibulo-spinal reflex.2We also analyzed vestibular afferences and efferences of Hoxb2 and Hoxa2 mutant mice and demonstrated presence of afferent and efferent endings. To this purpose, we are in the process of using newborn mutant pups to assess whether these projections are already lost at birth and whether new connections gradually appear during the first month of life.