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<p>Vestibular and spiral ganglion neurons (VGNs and SGNs) developed in the inner ear, where they extend fibers to innervate the vestibular and cochlear hair cells and project centrally to the vestibular and cochlear nuclei. This review focuses on representative molecular factors that regulate key processes in the development of inner ear neurons, including their specification, differentiation, axon targeting, and functional diversification. A temporal regulatory cascade defines the initial precursors through factors such as <i>Smarca4</i>, <i>Six1</i>, <i>Eya1</i>, followed by <i>Sox</i>2. While Sox2 deletion abolishes hair cell formation, a subset of inner ear neurons transiently develops but undergoes apoptosis before birth. In contrast, <i>Neurog1</i> deletion eliminates all ear-derived neurons but results in differential reductions in cochlear and vestibular hair cells. The development and survival of inner ear neurons depend on TrkB and TrkC signaling. Although deletion of <i>TrkB</i> and <i>TrkC</i> results in a complete loss of neurons, each shows distinct effects on VGN and SGN survival and innervation. Downstream of early transcriptional regulators, <i>Neurod1</i> and <i>Isl1</i> promote neuronal differentiation, survival, migration, and the formation of peripheral and central projections. The development of VGNs depends on at least two progenitor populations that give rise to three neuronal subtypes that differ in their innervation of vestibular hair cells but show incomplete segregation in the vestibular nuclei. In contrast, SGNs develop later and exhibit sequential segregation into four neuronal subtypes, corresponding to the two types of cochlear hair cells, with tonotopically organized projections to both the cochlea and cochlear nuclei.</p>

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Regulatory Networks Driving the Specification, Differentiation, and Diversification of Neurons in the Mouse Inner Ear

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月5日

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  • Gabriela Pavlinkova,
  • Pin-Xian Xu,
  • Kathryn S. E. Cheah,
  • Ebenezer N. Yamoah,
  • Bernd Fritzsch

摘要

Vestibular and spiral ganglion neurons (VGNs and SGNs) developed in the inner ear, where they extend fibers to innervate the vestibular and cochlear hair cells and project centrally to the vestibular and cochlear nuclei. This review focuses on representative molecular factors that regulate key processes in the development of inner ear neurons, including their specification, differentiation, axon targeting, and functional diversification. A temporal regulatory cascade defines the initial precursors through factors such as Smarca4, Six1, Eya1, followed by Sox2. While Sox2 deletion abolishes hair cell formation, a subset of inner ear neurons transiently develops but undergoes apoptosis before birth. In contrast, Neurog1 deletion eliminates all ear-derived neurons but results in differential reductions in cochlear and vestibular hair cells. The development and survival of inner ear neurons depend on TrkB and TrkC signaling. Although deletion of TrkB and TrkC results in a complete loss of neurons, each shows distinct effects on VGN and SGN survival and innervation. Downstream of early transcriptional regulators, Neurod1 and Isl1 promote neuronal differentiation, survival, migration, and the formation of peripheral and central projections. The development of VGNs depends on at least two progenitor populations that give rise to three neuronal subtypes that differ in their innervation of vestibular hair cells but show incomplete segregation in the vestibular nuclei. In contrast, SGNs develop later and exhibit sequential segregation into four neuronal subtypes, corresponding to the two types of cochlear hair cells, with tonotopically organized projections to both the cochlea and cochlear nuclei.