Spatial and Age-Dependent Hair Cell Generation in the Postnatal Mammalian Utricle
Spatial and Age-Dependent Hair Cell Generation in the Postnatal Mammalian Utricle
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DOI：
10.1007/s12035-015-9119-0
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发表时间：
2016-04-01
影响因子：
5.1
通讯作者：
Chen, Ping
中科院分区：
文献类型：
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作者：
Gao, Zhen;Kelly, Michael C.;Chen, Ping
前庭毛细胞的丧失是平衡障碍的常见原因。目前双侧前庭功能障碍的治疗选择有限。在发育过程中，无调性同源物 1 (Atoh1) 对于毛细胞的形成来说是充分且必需的，并提供了一个有前景的基因靶标来诱导哺乳动物毛细胞的生成。在这项研究中，我们使用转基因小鼠系来测试小鼠出生后椭圆囊中毛细胞诱导的年龄和细胞类型特异性。我们发现，在体内强制Atoh1表达可以诱导产后1至21天椭圆囊中毛细胞的形成，而随着动物年龄的增长，毛细胞诱导的功效逐渐降低。在椭圆囊中，毛细胞的诱导发生在感觉区域内和靠近感觉区域的移行上皮细胞中。在感觉上皮内，称为纹状体的中央区域最容易诱导毛细胞形成。此外，强制 Atoh1 表达可以以年龄依赖性方式促进增殖，这反映了出生后椭圆囊中毛细胞诱导功效的逐渐降低。这些结果表明，可以探索针对椭圆囊纹状体区域的细胞增殖和 Atoh1 来诱导哺乳动物的毛细胞再生。该研究还证明了动物模型的有用性，为前庭再生研究提供了体内 Atoh1 诱导模型。
Loss of vestibular hair cells is a common cause of balance disorders. Current treatment options for bilateral vestibular dysfunction are limited. During development, atonal homolog 1 (Atoh1) is sufficient and necessary for the formation of hair cells and provides a promising gene target to induce hair cell generation in the mammals. In this study, we used a transgenic mouse line to test the age and cell type specificity of hair cell induction in the postnatal utricle in mice. We found that forced Atoh1 expression in vivo can induce hair cell formation in the utricle from postnatal days 1 to 21, while the efficacy of hair cell induction is progressively reduced as the animals become older. In the utricle, the induction of hair cells occurs both within the sensory region and in cells in the transitional epithelium next to the sensory region. Within the sensory epithelium, the central region, known as the striola, is most subjective to the induction of hair cell formation. Furthermore, forced Atoh1 expression can promote proliferation in an age-dependent manner that mirrors the progressively reduced efficacy of hair cell induction in the postnatal utricle. These results suggest that targeting both cell proliferation and Atoh1 in the utricle striolar region may be explored to induce hair cell regeneration in mammals. The study also demonstrates the usefulness of the animal model that provides an in vivo Atoh1 induction model for vestibular regeneration studies.