The inner ear, which consists of the cochlea and vestibular systems, is a morphologically complex sensory organ. Hair cells, which serve as inner ear sensory cells, are critical for the transduction of mechanical stimulus into auditory and balance signals in the inner ear. After inner ear injury, auditory abnormalities and balance disorders are major conditions. Promoting hair cell regeneration is one of the most promising strategies to address hearing loss and vestibular dysfunction. Exploring the mechanism of inner ear development is the foundation for understanding the regeneration process of functional hair cells.
At embryonic day 8.5, the inner ear develops from the otocyst and undergoes significant morphological changes to form the final labyrinth structure. The Sonic hedgehog (Shh) signaling pathway is very important for the formation of cochlear structures. The absence of Shh causes the loss of cochlear. The Hmx2 and Hmx3 regulate the formation of the vestibular structure.
Scholars have made significant progress in understanding hair cell development and regeneration. Many genes that play important roles during inner ear development have been found in recent decades. For example, many studies have shown that transcription factor Atoh1 plays a positive regulatory role in hair cell development and differentiation. In embryonic mice, the lack of Atoh1 induces complete loss of both hair cells and associated supporting cells. Meanwhile, multiple signaling pathways, including Wnt, Notch, BMP/Smad, FGF and IGF signaling, have been found to involve in the regulation of inner ear development by controlling the expression of various transcription factors. Also, the interconnection and interaction between different pathways jointly form the signaling networks that regulate the development and regeneration of hair cells.
Many attempts have also been made to boost mammal hair cell regeneration, such as promoting proliferation and differentiation of pluripotent stem cells (IPS) and cochlear Lgr5-positive cells and inducing differentiation of embryonic stem cells (ESC) into otic progenitor cells. However, we are still quite far from fully understanding inner development and restoring hearing function. How do precursor cells gradually differentiate into different inner or outer hair cells? How different signaling pathways interact? What are the downstream target genes of atoh1? How to regenerate long-term surviving hair cells with a regular arrangement of cilia and effective connections to synapses? Biotechnology advancements such as transgenic mice expressing specific nuclear-and membrane-bound fluorescent proteins, high-resolution fluorescent imaging, gene-editing technology, single-cell RNAseq, will allow us to gain a much better understanding of these questions at both cellular and molecular levels.
Therefore, this research topic focuses on studying the cellular and molecular mechanism underlying the development and regeneration of inner ear hair cells. We welcome innovative studies that cover areas including but not limited to:
- Directional differentiation and maturation of hair cells
- Transcription factor regulation of inner ear hair cells.
- Signaling pathways that regulate inner ear development and regeneration.
- Epigenetic regulation in hair cell regeneration.
- Planar cell polarity (PCP) in the hair cells.
- Function and mechanism on deafness gene.
The inner ear, which consists of the cochlea and vestibular systems, is a morphologically complex sensory organ. Hair cells, which serve as inner ear sensory cells, are critical for the transduction of mechanical stimulus into auditory and balance signals in the inner ear. After inner ear injury, auditory abnormalities and balance disorders are major conditions. Promoting hair cell regeneration is one of the most promising strategies to address hearing loss and vestibular dysfunction. Exploring the mechanism of inner ear development is the foundation for understanding the regeneration process of functional hair cells.
At embryonic day 8.5, the inner ear develops from the otocyst and undergoes significant morphological changes to form the final labyrinth structure. The Sonic hedgehog (Shh) signaling pathway is very important for the formation of cochlear structures. The absence of Shh causes the loss of cochlear. The Hmx2 and Hmx3 regulate the formation of the vestibular structure.
Scholars have made significant progress in understanding hair cell development and regeneration. Many genes that play important roles during inner ear development have been found in recent decades. For example, many studies have shown that transcription factor Atoh1 plays a positive regulatory role in hair cell development and differentiation. In embryonic mice, the lack of Atoh1 induces complete loss of both hair cells and associated supporting cells. Meanwhile, multiple signaling pathways, including Wnt, Notch, BMP/Smad, FGF and IGF signaling, have been found to involve in the regulation of inner ear development by controlling the expression of various transcription factors. Also, the interconnection and interaction between different pathways jointly form the signaling networks that regulate the development and regeneration of hair cells.
Many attempts have also been made to boost mammal hair cell regeneration, such as promoting proliferation and differentiation of pluripotent stem cells (IPS) and cochlear Lgr5-positive cells and inducing differentiation of embryonic stem cells (ESC) into otic progenitor cells. However, we are still quite far from fully understanding inner development and restoring hearing function. How do precursor cells gradually differentiate into different inner or outer hair cells? How different signaling pathways interact? What are the downstream target genes of atoh1? How to regenerate long-term surviving hair cells with a regular arrangement of cilia and effective connections to synapses? Biotechnology advancements such as transgenic mice expressing specific nuclear-and membrane-bound fluorescent proteins, high-resolution fluorescent imaging, gene-editing technology, single-cell RNAseq, will allow us to gain a much better understanding of these questions at both cellular and molecular levels.
Therefore, this research topic focuses on studying the cellular and molecular mechanism underlying the development and regeneration of inner ear hair cells. We welcome innovative studies that cover areas including but not limited to:
- Directional differentiation and maturation of hair cells
- Transcription factor regulation of inner ear hair cells.
- Signaling pathways that regulate inner ear development and regeneration.
- Epigenetic regulation in hair cell regeneration.
- Planar cell polarity (PCP) in the hair cells.
- Function and mechanism on deafness gene.
