Selective expression of the NOSII isoform during mouse vestibulocochlear receptorgenesis

Based on in vitro studies, nitric oxide (NO) is reported to be involved in initial neuronal differentiation. In order to compare this finding with the situation in vivo, we have looked for the expression of the three NO synth ase isoforms in the developing mouse vestibulocochlear system. From these i soforms only the inducible NOS II is expressed during inner ear development . Examination of a series of embryonic and early postnatal animals, up to p ostnatal day 6, reveals a maturation-dependent, monophasic expression of th is isoform. Initial expression is observed by day 10 of gestation in nerve cells of the vestibolocochlear ganglion and on their fibres, By day 14 of g estation, these afferent fibres penetrate the epithelium of the prospective receptor fields making contact with early, differentiating immunoreactive cochlear hair cells and receptor cells of the macula and crista ampullaris. This receptor-cell-derived immunoreactivity vanished in differentiated sen sory hair cells by postnatal day 6, when both the constitutive isoforms and subsequent activated members of the down stream second messenger cascade ( guanylate cyclase/cGMP) of the adult mouse were not then detectable. The st rict phasic expression of NOS-II, independent of the second messenger syste m mentioned above, implies that there is a unique role for the inducible NO S isoform in nerve cell differentiation, independent of the NO/guanylate cy clase/cGMP pathway.