Segregating neural and mechanosensory fates in the developing ear: patterning, signaling, and transcriptional control


The vertebrate inner ear is composed of multiple sensory receptor epithelia, each of which is specialized for detection of sound, gravity, or angular acceleration. Each receptor epithelium contains mechanosensitive hair cells, which are connected to the brainstem by bipolar sensory neurons. Hair cells and their associated neurons are derived from the embryonic rudiment of the inner ear epithelium, but the precise spatial and temporal patterns of their generation, as well as the signals that coordinate these events, have only recently begun to be understood. Gene expression, lineage tracing, and mutant analyses suggest that both neurons and hair cells are generated from a common domain of neural and sensory competence in the embryonic inner ear rudiment. Members of the Shh, Wnt, and FGF families, together with retinoic acid signals, regulate transcription factor genes within the inner ear rudiment to establish the axial identity of the ear and regionalize neurogenic activity. Close-range signaling, such as that of the Notch pathway, specifies the fate of sensory regions and individual cell types. We also describe positive and negative interactions between basic helix-loop-helix and SoxB family transcription factors that specify either neuronal or sensory fates in a context-dependent manner. Finally, we review recent work on inner ear development in zebrafish, which demonstrates that the relative timing of neurogenesis and sensory epithelial formation is not phylogenetically constrained.

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Correspondence to Andrew K. Groves.

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Supplemental Material/Video: A video morph generated from serial section sets of mouse otocysts at three stages (24, 27, 30 somite stages; E9.5-E10) that were hybridized for detection of either Neurod1 (pink) or Tbx1 (blue) and reconstructed into space-filling models. The otocysts are viewed ventrally, as if through the second branchial arch, and oriented such that lateral is left, and anterior is up. The model at right renders the otocyst epithelium transparent to allow changes of Tbx1 expression in the dorsal otocyst to be visualized. Complementary patterning of Neurod1 and Tbx1 expression is maintained despite considerable changes in the extent of these domains over a 12-h developmental period. Still images used to generate this morph, as well as methods for generating the space-filling models, are presented in Raft et al. (2004). (MOV 1606 kb)


Supplemental Material/Video: A video morph generated from serial section sets of mouse otocysts at three stages (24, 27, 30 somite stages; E9.5-E10) that were hybridized for detection of either Neurod1 (pink) or Tbx1 (blue) and reconstructed into space-filling models. The otocysts are viewed ventrally, as if through the second branchial arch, and oriented such that lateral is left, and anterior is up. The model at right renders the otocyst epithelium transparent to allow changes of Tbx1 expression in the dorsal otocyst to be visualized. Complementary patterning of Neurod1 and Tbx1 expression is maintained despite considerable changes in the extent of these domains over a 12-h developmental period. Still images used to generate this morph, as well as methods for generating the space-filling models, are presented in Raft et al. (2004). (MOV 1606 kb)

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Raft, S., Groves, A.K. Segregating neural and mechanosensory fates in the developing ear: patterning, signaling, and transcriptional control. Cell Tissue Res 359, 315–332 (2015) doi:10.1007/s00441-014-1917-6

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  • Inner ear
  • Neurogenesis
  • Sensory cells
  • Transcription factors
  • Induction