Neuronal development proceeds in parallel with the morphogenesis of the inner ear (
Figure 3). All sensory organs of the inner ear and its associated sensory ganglia derive from a single embryonic source, the otic placode. The induction and morphogenesis of the inner ear from the otic placode represent highly orchestrated processes regulated by transcription factors and signaling molecules (reviewed by [
29,
30]). As the otic placode invaginates and forms the otocyst, neurogenesis is initiated by the expression of proneural bHLH transcription factor Neurogenin 1 (
Neurog1), which specifies neuronal precursors [
31], followed by the expression of another bHLH transcription factor,
Neurod1 [
32,
33]. The initial specification of the neuroblasts within the otic epithelium is followed by the delamination of neuroblasts from the anteroventral region of the otocyst as early as embryonic day nine (E9) in the mouse embryo. Soon after delamination, neuroblasts robustly express the bHLH gene
Neurod1, proliferate, and form a cochlea-vestibular ganglion (
Figure 3A,B). Neurons seem to be the first differentiated cells in the developing inner ear in all species examined; however, the inner ear structures, including the structures for hearing, vary among species [
34,
35]. A critical step in neurogenesis is the segregation of auditory and vestibular neurons, as the cochlea-vestibular ganglion segregates into a medial spiral ganglion and a lateral vestibular ganglion. The molecular cues regulating the specification and segregation of auditory and vestibular neurons are not fully understood. Current evidence indicates that the development of auditory and vestibular neurons is spatially and temporally segregated before or shortly after
Neurog1 expression (reviewed by [
36]). All neurons after a period of proliferation undergo their final cell divisions and begin to differentiate [
37]. As neurons mature, postmitotic auditory and vestibular neurons extend their processes to their peripheral targets (the organ of Corti and the five vestibular sensory epithelia) and to the central targets (the cochlear and vestibular nuclei of the brain stem). The central projections of the inner ear neurons reach the hindbrain as early as E11.5 in the mouse [
38,
39]. E12.5 is the earliest embryonic day to detect segregated central projections of auditory neurons to the cochlear nucleus from the vestibular nerve in the mouse [
38,
39]. This is a time before the peripheral projections reach their targets. Auditory neurons mature and extend their peripheral neurites, starting in the base of the cochlea, around E12.5 in the mouse [
21,
39,
40]. Auditory neurons express two neurotrophin receptors, TrkB and TrkC, depending on their position along the axis of the cochlea, suggesting that these molecular differences in axons from different regions of the cochlea guide the topographic map formation [
21]. Both receptors present in the developing auditory neurons and their respective neurotrophins (BDNF and NT-3), expressed by the sensory epithelia, are crucial not only for axon guidance but, overall, for neuronal survival, as well as synaptogenesis and the maturation of firing properties (reviewed in [
22]).