Development and Evolution of the Vertebrate Ear's Neurosensory System

Abstract

Ear development transforms an area of head ectoderm into a complex three‐dimensional structure carrying three types of sensory systems for gravistatic and angular acceleration sensation as well as hearing. Transformation of the otic ectoderm starts with the specification of neurosensory cells that differentiate into the essential components for the sensory processes, the hair cells, supporting cells and neurons. The role of proneural bHLH genes in this process is presented and put into the context of ear evolution to appreciate how cellular diversity is embedded into the diversification of the ear as whole as well as the evolution of novel sensory capacities in the ear. Ear neurosensory development is characterised by extensive cross‐regulation of multiple factors for cell type specification and fate fixation. Data suggesting that sensory epithelia may directly regulate the formation of their associated structures to guide specific stimuli to the sensory epithelia are presented.

Key Concepts:

  • Numerous coexpressed factors regulate transformation of general epidermis to prosensory otic ectoderm.

  • Proneural basic‐Helix–Loop–Helix proteins define cell fate through cross‐regulative interaction.

  • Sensory epithelia regulate formation of accessory structures including aspects of ear morphogenesis.

  • Ear development can best be understood in the context of ear evolution.

Keywords: ear development; neurosensory development; auditory system development

Figure 1.

The morphogenesis, clonal expansion and cellular interactions underlying mammalian ear development. (a) The ear develops from the otic placode, which in turn is induced to increase proliferation, invaginate to form the otocyst and undergo morphogenesis into the ear with the six sensory organs through multiple signals such as FGFs, SHH, WNTs and BMP's. (b) and top left in (b), Embedded within the complex morphogenesis of the ear is the selection of prosensory precursor cells that give rise through clonal expansion to all sensory neurons and sensory hair cells of the ear's six sensory epithelia. Prosensory precursors are multipotent stem cells that will, through asymmetric divisions, generate sensory neuron precursors that in turn will differentiate into neuronal precursors that will develop into neurons. Some of the sensory neuron precursor cells will also give rise to sensory epithelia precursors, which ultimately differentiate into hair cells and supporting cells. This selection of the prosensory precursor could in theory pick a single cell which, through clonal expansion and 15 divisions over the next six days, could possibly give rise to all neurosensory cells and supporting cells of the ear. (c) The known and suspected signalling pathways transforming an ectodermal cell into an otocyst cell are shown (left) followed by the gene upregulation in the prosensory precursor stem cell (left centre). On the right, the molecular interactions are shown, which help, through lateral inhibition and the upregulation of Hes genes through the Delta/Notch system, to stabilise the differentiation of supporting cells. Neuron and hair cell differentiation in turn is driven by the upregulation of specific bHLH genes (Neurod1 for neurons and Atoh1 for hair cells). Arrows interconnecting horizontal panels show the relative origin of various cell types in this hypothetical process that progressively limits the cell differentiation capacity. Modified after Fritzsch et al. .

Figure 2.

The inner ear of mammals with six sensory epithelia, including the coiled cochlea, evolved from simple beginnings as exemplified by the hagfish's ear. These ears are formed by a simple torus with two ring‐shaped sensory epithelia for angular acceleration (green) around the anterior and posterior canal and a single epithelium for gravistatic reception (blue). All vertebrate ears have a single ganglion, some degree of gravistatic organ segregation (two to three blue patches) and two canals with canal cristae. A major addition in evolution is the formation of the horizontal canal and crista (purple), which appears to depend on at least two genes Otx1 and Foxg1. The ear evolved up to nine sensory end organs in some amphibians and may have formed the basilar papilla in the sarcopterygian ancestor of land vertebrates (red), which gave rise to the organ of Corti in the mammalian cochlea.

Figure 3.

The interrelationship of ear‐relevant bHLH genes (a) and the hypothetical evolution of sensory cells with and without axons (b) is shown. Achaete/scute sequence is used as a neuronal ingroup; other bHLH gene clades are used as outgroups. Note that Nhlh are in between the achaete/scute and the atonal family of genes. Most triploblasts have representatives of all three atonal gene family members, Atoh, Neurog and Neurod, except for the fly (Drosophila melanogaster; Dm), which lacks Neurod1. As both lophotrochozoans (Lg, a snail) and trochozoans (Pdu, a polychaete) have members of all three atonal families, flies must have secondarily lost Neurod and reduced the function of Neurog. Most ecdysozoan animals have sensory cells with an axon, whereas vertebrates have axonless hair cells and an ear‐derived sensory neuron that connects the hair cell with the brain. It is conceivable that the apparent multiplication of bHLH genes in ancestral triploblasts provided the molecular basis for cellular diversification exemplified by the vertebrate ear's developmental programme. Modified after Fritzsch et al. .

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Further Reading

Giraldez F and Fritzsch B (2007) Special edition: development of the ear. International Journal of Developmental Biology 51: 429–687.

Kelley MW, Wu DK, Popper AN and Fay RR (2005) Development of the Inner Ear. Heidelberg: Springer Verlag. SHAR series.

Romand R and Varela‐Nieto I (2003) Special Edition: development of the auditory and vestibular systems. Current Topics in Developmental Biology 57: 1–489.

Unsicker K and Kriegelstein K (2005) Cell signaling and growth factors in development. Weinheim: Wiley‐VCH.

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Fritzsch, Bernd, and Crapon de Caprona, Marie‐Dominique(Oct 2010) Development and Evolution of the Vertebrate Ear's Neurosensory System. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0020917]