PAX2 CONTRIBUTES TO INNER-EAR PATTERNING AND OPTIC-NERVE TRAJECTORY

During gestation, the paired box-containing gene Pax2 is expressed in the mid-hindbrain area, developing eye and inner ear. We generated Pax 2 null mutant mice, which show the requirement of Pax2 for the establi shment of axonal pathways along the optic stalks and ventral diencepha lon. In mutant brains, the optic tracts remain totally ipsilateral due to agenesis of the optic chiasma. Furthermore, Pax2 mutants show exte nsion of the pigmented retina into the optic stalks and failure of the optic fissure to close resulting in coloboma. In the inner ear, Pax2 mutants show agenesis of the cochlea and the spiral ganglion, i.e., th e parts of the organ responsible for auditory function and in whose pr imordium Pax2 is expressed. Our results identify Pax2 as a major regul ator of patterning during organogenesis of the eye and inner ear and i ndicate its function in morphogenetic events required for closure of t he optic fissure and neural tube.