Temporal coupling between specifications of neuronal and macular fates of the inner ear

Abstract

The inner ear is a complex organ comprised of various specialized sensory organs for detecting sound and head movements. The timing of specification for these sensory organs, however, is not clear. Previous fate mapping results of the inner ear indicate that vestibular and auditory ganglia and two of the vestibular sensory organs, the utricular macula (UM) and saccular macula (SM), are lineage related. Based on the medial-lateral relationship where respective auditory and vestibular neuroblasts exit from the otic epithelium and the subsequent formation of the medial SM and lateral UM in these regions, we hypothesized that specification of the two lateral structures, the vestibular ganglion and the UM are coupled and likewise for the two medial structures, the auditory ganglion and the SM. We tested this hypothesis by surgically inverting the primary axes of the otic cup in ovo and investigating the fate of the vestibular neurogenic region, which had been spotted with a lipophilic dye. Our results showed that the laterally-positioned, dye-associated, vestibular ganglion and UM were largely normal in transplanted ears, whereas both auditory ganglion and SM showed abnormalities suggesting the lateral but not the medial-derived structures were mostly specified at the time of transplantation. Both of these results are consistent with a temporal coupling between neuronal and macular fate specifications.

Origin of Neuroblasts in the Avian Otic Placode and Their Distributions in the Acoustic and Vestibular Ganglia

“…It has also been suggested that neuroblasts constituting the developing AG and VG could be specified before they leave the otic epithelium, in two contiguous domains within the ventral wall of the otic vesicle. These two areas are separated by a medio-lateral boundary and associated with the utricular and saccular maculae, respectively [ 34 , 41 ]. The VG and the utricular macula are specified before the AG and saccular macula at the otic cup stage [ 41 ].…”

“…These two areas are separated by a medio-lateral boundary and associated with the utricular and saccular maculae, respectively [ 34 , 41 ]. The VG and the utricular macula are specified before the AG and saccular macula at the otic cup stage [ 41 ]. The subdivision of the neurogenic domain into vestibular and auditory regions was also suggested when analyzing the expression of relevant neural markers.…”

“…When development proceeds, delaminating neuroblasts, Islet1/2 -positive, are detected exclusively in a narrow stripe located along the border of the Fgf10 -labeling domain at the late otic cup stage [ 24 , 34 ]. At the otic vesicle stage, neurogenesis occurs in the anteroventral wall of the otocyst [ 21 , 22 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 ]. Thus, intense otic neurogenesis takes place in the presumptive areas of the utricular and saccular maculae [ 12 , 13 , 19 ].…”

“…Using a Ngn1-CreER T2 transgenic mouse line, it was reported that early Neurog1 -expressing cells mostly give rise to the vestibular neurons, whereas the late Neurog1 -expressing cells predominantly generate cochlear neurons [ 53 ]. A spatial relationship between subpopulations of otic neurons and developing sensory patches was also suggested, such that the specification of the vestibular neurons and the utricular macula are coupled, as are the auditory neurons and the saccular macula [ 34 , 41 ]. In addition, studies on chick development have shown that the precursors of auditory and vestibular cells are regionally segregated in the epithelium of the otic placode/cup, with vestibular neurons being generated in its anterior-lateral portion, while auditory neurons are originated in its posterior-medial region [ 54 ].…”