Gene, cell, and organ multiplication drives inner ear evolution

Abstract

We review the development and evolution of the ear neurosensory cells, the aggregation of neurosensory cells into an otic placode, the evolution of novel neurosensory structures dedicated to hearing and the evolution of novel nuclei and their input dedicated to processing those novel auditory stimuli. The evolution of the apparently novel auditory system lies in duplication and diversification of cell fate transcription regulation that allows variation at the cellular level [transforming a single neurosensory cell into a sensory cell connected to its targets by a sensory neuron as well as diversifying hair cells], organ level [duplication of organ development followed by diversification and novel stimulus acquisition] and brain nuclear level [multiplication of transcription factors to regulate various neuron and neuron aggregate fate to transform the spinal cord into the unique hindbrain organization]. Tying cell fate changes driven by bHLH and other transcription factors into cell and organ changes is at the moment tentative as not all relevant factors are known and their gene regulatory network is only rudimentary understood. Future research can use the blueprint proposed here to provide both the deeper molecular evolutionary understanding as well as a more detailed appreciation of developmental networks. This understanding can reveal how an auditory system evolved through transformation of existing cell fate determining networks and thus how neurosensory evolution occurred through molecular changes affecting cell fate decision processes. Appreciating the evolutionary cascade of developmental program changes could allow identifying essential steps needed to restore cells and organs in the future.

Ear transplantations reveal conservation of inner ear afferent pathfinding cues

“…Since inner ear afferents project to the same dorsoventral location within the hindbrains across all vertebrates 4 , 18 , we assume that all neural crest and placode derived cranial nerve afferents are navigating in the hindbrain using a conserved set of guidance molecules. Given the conservation of transcription factors and expression of diffusible molecules, such as Wnt, BMP, and Shh, across species and between the hindbrain and spinal cord 24 , 25 , we used a novel approach to investigate whether presumed conserved guidance molecules may play a role in the initial targeting of inner ear afferents through heterochronic, xenoplastic, and heterotopic transplantations in chickens and mice. We tested if these presumably conserved morphogens can guide mouse inner ear afferents in a chicken hindbrain despite over 300 million years of independent ear and brain evolution of these two lines of amniotes 26 .…”

Growth factor and receptor malfunctions associated with human genetic deafness

“…Impaired sound detection is a prevalent deficit of older adults as well as for one in 500 to one in 2000 young children . Deficits in hearing often result from dysfunction of one of the complex, delicate structures or intricate signaling pathways in the inner ear . Hearing loss can be conductive, sensorineural or mixed, depending on whether the defect is in the middle ear, inner ear or both, respectively (Figure A).…”

“…1,2 Deficits in hearing often result from dysfunction of one of the complex, delicate structures or intricate signaling pathways in the inner ear. 3 Hearing loss can be conductive, sensorineural or mixed, depending on whether the defect is in the middle ear, inner ear or both, respectively ( Figure 1A). The complex structure of inner ear develops from the otic placode next to the hindbrain, 4 which invaginates to form the otic vesicle ( Figure 1B).…”

Transplantation of Ears Provides Insights into Inner Ear Afferent Pathfinding Properties

“…The central navigational properties of developing inner ear afferents is incompletely understood (Maklad and Fritzsch, ), but can be partially derailed in mutants of certain transcription factors such as Neurod1 (Jahan et al, ) and several others (Goodrich, ). In addition, afferent projections are established in a spatiotemporal progressing manner (Fritzsch et al, ; Zecca et al, ) likely using Wnt gradients to navigate (Fritzsch and Elliott, ; Yang et al, ) and can do so even if target nuclei are molecularly ablated (Elliott et al, ).…”