Fig. 8. Schematics illustrating inner ear defects and genetic interactions revealed by analysis of Brn3a mutant mice. (A) Inner ear defects in Brn3a^-/- mice. In the mutant, the spiral ganglion (SG) loses 30% of neurons by P0, whereas the vestibular ganglion (VG) contains normal number of neurons. Substantial reduction in soma size of neurons is seen in both Brn3a^-/- SG and VG. In addition, the mutant SG neurons are defective in migration and thus do not become clustered. In the mutant cochlea (Co), there is overall decrease in afferent fiber density in the basal turn with a nearly complete loss of innervation at the base (broken green arrow). Moreover, efferent innervation displays profound pathfinding defects throughout the entire cochlea. In the mutant vestibular system, the saccule (S), utricle (U), and anterior vertical (AVC) and horizontal (HC) canals are all well innervated by afferent fibers. However, the posterior vertical canal (PVC) lacks afferent innervation (broken pink arrow). (B) Genetic interactions between Brn3a and other transcriptional regulators during sensory gangliogenesis. Brn3a is required for differentiation and survival of sensory neurons in the trigeminal (TG), spiral, vestibular, geniculate (GG) and dorsal root (DRG) ganglia. For fate commitment of neuron progenitors, the TG, SG and VG require Ngn1; the GG requires Ngn2; and the DRG requires both Ngn1 and Ngn2. Therefore, Ngn1 and Ngn2 genetically act upstream of Brn3a. Brn3a regulates expression of TrkA, TrkB, TrkC, Brn3b and Brn3c in TG and DRG, and that of parvalbumin (Parv) and Brn3b in SG and VG. In addition, it controls Brn3b expression in GG, and TrkC expression in SG. During GG development, Phox2a also genetically acts downstream of Ngn2 as it is only required for differentiation and survival of GG neurons. Phox2a has been shown to control expression of c-Ret and dopamine-ß-hydroxylase (DBH) in GG.