Atoh1 expression defines activated progenitors and differentiating hair cells during avian hair cell regeneration
Atoh1 expression defines activated progenitors and differentiating hair cells during avian hair cell regeneration
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DOI：
10.1002/dvdy.21023
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发表时间：
2007-01-01
影响因子：
2.5
通讯作者：
Stone, Jennifer S.
中科院分区：
文献类型：
--
作者：
Cafaro, Jon;Lee, Gi Soo;Stone, Jennifer S.
在鸟类内耳中，非感觉性支持细胞通过两种不同的过程产生新的感觉性毛细胞：有丝分裂和直接转分化。鸟类毛细胞再生过程中支持细胞行为的调控以及细胞命运特化的特征尚不明确。利用免疫荧光技术在成年鸡静止和再生的毛细胞上皮中检测了Atoh1的表达，Atoh1是一种在发育过程中对毛细胞特化必要且充分的前神经转录因子。在未处理的鸡中，在静止的听觉上皮中未检测到Atoh1蛋白。相比之下，在不断进行毛细胞更替的椭圆囊斑中可以看到许多Atoh1阳性的细胞核。在耳毒性药物给药后15小时，在明显的毛细胞损伤和支持细胞重新进入细胞周期之前，听觉上皮中就出现了Atoh1阳性的细胞核。随后，在15%的分裂支持细胞中可以看到Atoh1标记。在细胞分裂过程中，Atoh1对称地分布在子细胞中，但此后不久Atoh1的水平受到显著调控。细胞分化后，Atoh1标记局限于通过有丝分裂或直接转分化再生的毛细胞。然而，分裂祖细胞中的Atoh1表达并不一定能预测子细胞的毛细胞命运特化。最后，毛细胞再生的主要模式在听觉上皮的径向轴上有显著差异，有丝分裂在神经侧最常见，直接转分化在非神经侧最常见。这些观察结果表明，在成年鸡耳的毛细胞再生过程中，Atoh1在重新特化支持细胞以及使有丝分裂后的细胞偏向毛细胞命运方面发挥作用。
In the avian inner ear, nonsensory supporting cells give rise to new sensory hair cells through two distinct processes: mitosis and direct transdifferentiation. Regulation of supporting cell behavior and cell fate specification during avian hair cell regeneration is poorly characterized. Expression of Atoh1, a proneural transcription factor necessary and sufficient for developmental hair cell specification, was examined using immunofluorescence in quiescent and regenerating hair cell epithelia of mature chickens. In untreated birds, Atoh1 protein was not detected in the auditory epithelium, which is quiescent. In contrast, numerous Atoh1-positive nuclei were seen in the utricular macula, which undergoes continual hair cell turnover. Atoh1-positive nuclei emerged in the auditory epithelium by 15 hr post-ototoxin administration, before overt hair cell damage and supporting cell re-entry into the cell cycle. Subsequently, Atoh1 labeling was seen in 15% of dividing supporting cells. During cell division, Atoh1 was distributed symmetrically to daughter cells, but Atoh1 levels were dramatically regulated shortly thereafter. After cellular differentiation, Atoh1 labeling was confined to hair cells regenerated through either mitosis or direct transdifferentiation. However, Atoh1 expression in dividing progenitors did not necessarily predict hair cell fate specification in daughter cells. Finally, predominant modes of hair cell regeneration varied significantly across the radial axis of the auditory epithelium, with mitosis most frequent neurally and direct transdifferentiation most frequent abneurally. These observations suggest a role for Atoh1 in respecifying supporting cells and in biasing postmitotic cells toward the hair cell fate during hair cell regeneration in the mature chicken ear.