The development of the vertebrate inner ear

Abstract

The inner ear is a complex sensory organ responsible for balance and sound detection in vertebrates. It originates from a transient embryonic structure, the otic vesicle, that contains all of the information to develop autonomously into the mature inner ear. We review here the development of the otic vesicle, bringing together classical embryological experiments and recent genetic and molecular data. The specification of the prospective ectoderm and its commitment to the otic fate are very early events and can be related to the expression of genes with restricted expression domains. A combinatorial gene expression model for placode specification and diversification, based on classical embryological evidence and gene expression patterns, is discussed. The formation of the otic vesicle is dependent on inducing signals from endoderm, mesoderm and neuroectoderm. Ear induction consists of a sequence of discrete instructions from those tissues that confer its final identity on the otic field, rather than a single all-or-none process. The important role of the neural tube in otic development is highlighted by the abnormalities observed in mouse mutants for the Hoxa1, kreisler and fgf3 genes and those reported in retinoic acid-deficient quails. Still, the nature of the relation between the neural tube and otic development remains unclear. Gene targeting experiments in the mouse have provided evidence for genes potentially involved in regional and cell-fate specification in the inner ear. The disruption of the mouse Brn3.1 gene identifies the first mutation affecting sensory hair-cell specification, and mutants for Pax2 and Nkx5.1 genes show their requirement for the development of specific regions of the otic vesicle. Several growth-factors contribute to the patterned cell proliferation of the otic vesicle. Among these, IGF-I and FGF-2 are expressed in the otic vesicle and may act in an autocrine manner. Finally, little is known about early mechanisms involved in guiding ear innervation. However, targeted disruption of genes coding for neurotrophins and Trk receptors have shown that once synaptic contacts are established, they depend on specific trophic interactions that involve these two gene families. The accessibility of new cellular and molecular approaches are opening new perspectives in vertebrate development and are also starting to be applied to ear development. This will allow this classical and attractive model system to see a rapid progress in the near future.

Cranial expression of class 3 secreted semaphorins and their neuropilin receptors

“…The dorsolateral otic vesicle gives rise to the vestibular organ, whereas the ventromedial half forms the cochlear. Many genes that determine this differentiation are already localised to specific areas of the otic vesicle before any obvious morphologic changes are apparent (Torres and Giraldez, 1998;Merlo et al, 2002). We find that NPN1 and several of the semaphorins are also clearly restricted to certain regions of this pseudostratified epithelium.…”

“…This finding raises the possibility that NPN1 and Sema3D are downstream targets of these transcription factors. However, as more factors are found to be restricted to specific areas of the otic vesicle and thereafter required for the development of specific facets of the auditory and vestibular systems (Torres and Giraldez, 1998), it will be important to investigate the role of semaphorins in the regulation of morphogenesis and innervation.…”

Genetic interactions underlying otic placode induction and formation

“…The vertebrate inner ear develops from the otic placode, a transient thickening of ectodermal epithelium that forms at the edge of the neural plate during mid-somitogenesis and invaginates to form the otic vesicle (Torres and Giraldez, 1998;Baker and Bronner-Fraser, 2001;Noramly and Grainger, 2002). Transplantation experiments, together with molecular and morphological evidence, suggest that competence of the ectoderm to form an otic placode is distributed within an extended region along the neural plate/epidermal border during gastrulation and early neurulation (Yntema, 1933;Waddington, 1937;Meier, 1978;Gallagher et al, 1996;Groves and Bronner-Fraser, 2000).…”

OC29 is preferentially expressed in the presumptive sensory organ region of the otocyst

“…A great number of genes, including those encoding transcription factors, growth factors, and membrane receptors, have been identified in the developing inner ear over the past few decades (Torres and Giraldez, 1998;Bryant et al, 2002;Noramly and Grainger, 2002). Most of them show relatively broad but asymmetric expression patterns in the otocyst (Torres and Giraldez, 1998;Represa et al, 2000).…”

“…Most of them show relatively broad but asymmetric expression patterns in the otocyst (Torres and Giraldez, 1998;Represa et al, 2000). For example, Hmx3 is expressed dorsolaterally (Rinkwitz-Brandt et al, 1995, 1996Herbrand et al, 1998;Wang et al, 2000), whereas Pax2 is expressed medially (Nornes et al, 1990;Rinkwitz-Brandt et al, 1996;Herbrand et al, 1998;Lawoko-Kerali et al, 2002).…”