How to Bury the Dead: Elimination of Apoptotic Hair Cells from the Hearing Organ of the Mouse
How to Bury the Dead: Elimination of Apoptotic Hair Cells from the Hearing Organ of the Mouse
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DOI：
10.1007/s10162-014-0480-x
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发表时间：
2014-12-01
影响因子：
2.4
通讯作者：
Pirvola, Ulla
中科院分区：
文献类型：
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作者：
Anttonen, Tommi;Belevich, Ilya;Pirvola, Ulla
毛细胞死亡是听力损伤的主要原因。在毛细胞损失时保持表面屏障对于防止富钾内淋巴渗漏到Corti器官中和防止细胞损伤扩大至关重要。了解这个细胞结构复杂的器官中的伤口愈合需要超微结构3D可视化。本研究利用连续块面扫描电子显微镜技术，深入研究了耳毒性损伤后耳蜗外毛细胞和神经胶质样Deiters细胞急性反应的细胞生物学机制。我们表明，代特斯细胞的功能作为吞噬细胞。创伤后，它们的指骨突起肿胀，由此产生的紧密细胞接触允许凋亡细胞碎片的吞噬。内耳感觉上皮细胞的顶端结构域死亡的毛细胞被消除，这一事件被认为取决于支持细胞的肌动球蛋白收缩活性。我们表明，在凋亡的外毛细胞的Corti器官的情况下，消除其顶点之前，强烈的细胞体收缩，强调的作用，垂死的细胞本身的分裂。我们的数据表明，重新密封上皮表面的连接延伸的Deiters细胞是动态增强的新聚合的F-肌动蛋白带。通过分析Cdc 42失活的Deiters细胞与缺陷的肌动蛋白动力学和表面封闭，我们表明，受损的屏障完整性转移毛细胞死亡从凋亡到坏死，并导致扩大毛细胞和神经纤维损伤。我们的研究结果具有治疗保护和再生干预的影响，因为这两种干预措施应保持屏障的完整性。
Hair cell death is a major cause of hearing impairment. Preservation of surface barrier upon hair cell loss is critical to prevent leakage of potassium-rich endolymph into the organ of Corti and to prevent expansion of cellular damage. Understanding of wound healing in this cytoarchitecturally complex organ requires ultrastructural 3D visualization. Powered by the serial block-face scanning electron microscopy, we penetrate into the cell biological mechanisms in the acute response of outer hair cells and glial-like Deiters' cells to ototoxic trauma in vivo. We show that Deiters' cells function as phagocytes. Upon trauma, their phalangeal processes swell and the resulting close cellular contacts allow engulfment of apoptotic cell debris. Apical domains of dying hair cells are eliminated from the inner ear sensory epithelia, an event thought to depend on supporting cells' actomyosin contractile activity. We show that in the case of apoptotic outer hair cells of the organ of Corti, elimination of their apices is preceded by strong cell body shrinkage, emphasizing the role of the dying cell itself in the cleavage. Our data reveal that the resealing of epithelial surface by junctional extensions of Deiters' cells is dynamically reinforced by newly polymerized F-actin belts. By analyzing Cdc42-inactivated Deiters' cells with defects in actin dynamics and surface closure, we show that compromised barrier integrity shifts hair cell death from apoptosis to necrosis and leads to expanded hair cell and nerve fiber damage. Our results have implications concerning therapeutic protective and regenerative interventions, because both interventions should maintain barrier integrity.