The pattern of innervations at E11.5 and E13.5. Innervation of the ear in terms of distinct fibers to sensory epithelia develops around E11.5 in wild-type mice (A). In Pax2;8 double null mutants there is at least a transient projection to a small otocyst which never develops any distinct projection pattern to the otocyst. At later stages, Pax2;8 double null mice have only an ear vesicle without any feature that is completely devoid of any afferent or efferent innervation (E, compare to C, D). In contrast, Pax2; Pax8 double heterozygote (C) and Pax8 null mouse (F) show at E13.5 fibers reaching to the posterior crista (PC) and the spiral ganglia (Sg) extend some fibers to the developing organ of Corti (OC). In contrast, fibers to the PC are reduced in Pax2 null mice, the saccular innervation is diffuse and there is little extension of afferent (D) or efferent (G) nerve fibers to the cochlea. Note the similarities in distribution of afferents (D) and efferents (G) in these two Pax2 null mice indicating a consistent but different pattern of innervation for these mutants. Injection of dye selectively into the otocyst reveals a few fibers extending toward the brain from the region of this presumptive cochlea (H). These data suggest that at least some early development of the cochlea neurons occurs but that the overall development or projection to the brain is severely truncated. OC, organ of Corti; PC, posterior crista; SG, spiral ganglion; VG, vestibular ganglion; VII, facial nerve, Bar indicates 100 um.