Cells, molecules and morphogenesis: the making of the vertebrate ear

Abstract

The development and evolution of mechanosensory cells and the vertebrate ear is reviewed with an emphasis on delineating the cellular, molecular and developmental basis of these changes. Outgroup comparisons suggests that mechanosensory cells are ancient features of multicellular organisms. Molecular evidence suggests that key genes involved in mechanosensory cell function and development are also conserved among metazoans. The divergent morphology of mechanosensory cells across phyla is interpreted here as 'deep molecular homology' that was in parallel shaped into different forms in each lineage. The vertebrate mechanosensory hair cell and its associated neuron are interpreted as uniquely derived features of vertebrates. It is proposed that the vertebrate otic placode presents a unique embryonic adaptation in which the diffusely distributed ancestral mechanosensory cells became concentrated to generate a large neurosensory precursor population. Morphogenesis of the inner ear is reviewed and shown to depend on genes expressed in and around the hindbrain that interact with the otic placode to define boundaries and polarities. These patterning genes affect downstream genes needed to maintain proliferation and to execute ear morphogenesis. We propose that fibroblast growth factors (FGFs) and their receptors (FGFRs) are a crucial central node to translate patterning into the complex morphology of the vertebrate ear. Unfortunately, the FGF and FGFR genes have not been fully analyzed in the many mutants with morphogenetic ear defects described thus far. Likewise, little information exists on the ear histogenesis and neurogenesis in many mutants. Nevertheless, a molecular mechanism is now emerging for the formation of the horizontal canal, an evolutionary novelty of the gnathostome ear. The existing general module mediating vertical canal growth and morphogenesis was modified by two sets of new genes: one set responsible for horizontal canal morphogenesis and another set for neurosensory formation of the horizontal crista and associated sensory neurons. The dramatic progress in deciphering the molecular basis of ear morphogenesis offers grounds for optimism for translational research toward intervention in human morphogenetic defects of the ear.

Molecular evolution of the vertebrate mechanosensory cell and ear

“…Specifically, atonal genes evolved with multicellular organisms (Seipel et al, 2004) and are among a few protein coding genes that are structurally and functionally conserved to the extent that orthologues of fly and mouse, atonal and Atoh1, can be mutually exchanged and show compensatory function in distant organisms (Wang et al, 2002). The bHLH family shows expansion consistent with the requirement of additional members to regulate differentiation of developmentally and physically connected cells in vertebrates, the sensory neurons and hair cells , Fritzsch et al, 2006b). The best known downstream factor of atonal genes is Barlh, a gene necessary to maintain hair cells which are progressively lost in null mutantsÄ (Li et al, 2002).…”

“…Combined with the strong evidence of evolutionary ancestry of many cellular transcription factors and possibly certain components for the tethering of the mechanosensory transducer channel outlined above, it appears possible that hair cells of chordates represent a uniquely derived feature of an ancestral theme of mechanosensory cells and can be traced back to mechanosensory cells of coelenterates that also show some degree of asymmetric development (Fritzsch et al, 2006b). The grouping of these molecular and anatomical features make it increasingly less likely that mechanosensory cells arose through independent evolutionary events as previously suggested based on fewer data (Coffin et al, 2004).…”

“…Indeed, in many chordates and also in amphioxus there is distribution of single sensory cells in the skin, suggesting that the capacity of the skin to generate diffusely distributed sensory cells is not fully suppressed in these species or may be the only sensory arrangement (Fritzsch et al, 2006b, Holland, 2005. Moreover, it appears that such concentration of sensory precursors evolved independently several times in metazoans but might use only a limited set of conserved transcription factors to do so thus leading to a false impression of homology that is largely based on the common and ancestral, cellular development regulating transcription factors.…”

“…Statocysts are known for many taxa of metazoans, but a lateral line system is restricted to few. Modified after (Arkett et al, 1988, Budelmann, 1989, Burighel et al, 2003, Fritzsch et al, 2006b, Jorgensen, 1989, Steenkamp et al, 2006, Todi et al, 2005.…”

Origin of Inner Ear Hair Cells: Morphological and Functional Differentiation from Ciliary Cells into Hair Cells in Zebrafish Inner Ear

“…The apical specialization of invertebrate mechanosensory cells contrasts with the staircaselike arrangement of actin-based stereocilia associated with a single kinocilium in vertebrate hair cells (Fritzsch et al, 2006(Fritzsch et al, , 2007. In arthropods, for example, mechanoreceptors in chordotonal organs possess a single cilium without actin-based microvilli (Caldwell and Eberl, 2002), although there are some exceptions (e.g., hair cells with a directional collar of microvilli in jellyfish and ascidians (Arkett et al, 1988;Manni et al, 2004)).…”