Brn3a is a transcriptional regulator of soma size, target field innervation and axon pathfinding of inner ear sensory neurons

The POU domain transcription factors Brn3a, Brn3b and Brn3c are required fo r the proper development of sensory ganglia, retinal ganglion cells, and in ner ear hair cells, respectively. We have investigated the roles of Brn3a i n neuronal differentiation and target innervation in the facial-stato-acous tic ganglion. We show that absence of Brn3a results in a substantial reduct ion in neuronal size, abnormal neuronal migration and downregulation of gen e expression, including that of the neurotrophin receptor TrkC, parvalbumin and Brn3b. Selective loss of TrkC neurons in the spiral ganglion of Brn3a( -/-) cochlea leads to an innervation defect similar to that of TrkC(-/-) mi ce. Most remarkably, our results uncover a novel role for Brn3a in regulati ng axon pathfinding and target field innervation by spiral and vestibular g anglion neurons. Loss of Brn3a results in severe retardation in development of the axon projections to the cochlea and the posterior vertical canal as early as E13,5. In addition, efferent axons that use the afferent fibers a s a scaffold during pathfinding also show severe misrouting. Interestingly, despite the well-established roles of ephrins and EphB receptors in axon p athfinding, expression of these molecules does not appear to be affected in Brn3a(-/-) mice. Thus, Brn3a must control additional downstream genes that are required for axon pathfinding.