Kwan Tao, White Patricia M, Segil Neil
House Ear Institute, Gonda Division of Cell Biology and Genetics, Los Angeles, California, USA.
Ann N Y Acad Sci. 2009 Jul;1170:28-33. doi: 10.1111/j.1749-6632.2009.04484.x.
Loss of sensory hair cells is the leading cause of deafness in humans. The mammalian cochlea cannot regenerate its complement of sensory hair cells. Thus at present, the only treatment for deafness due to sensory hair cell loss is the use of prosthetics, such as hearing aids and cochlear implants. In contrast, in nonmammalian vertebrates, such as birds, hair cell regeneration occurs following the death of hair cells and leads to the restoration of hearing. Regeneration in birds is successful because supporting cells that surround the hair cells can divide and are able to subsequently differentiate into new hair cells. However, supporting cells in mammals do not normally divide or transdifferentiate when hair cells are lost, and so regeneration does not occur. To understand the failure of mammalian cochlear hair cell regeneration, we need to understand the molecular mechanisms that underlie cell division control and hair cell differentiation, both during embryogenesis and in the postnatal mouse. In this review, we present a discussion of the regulation of cell proliferation in embryogenesis and during postnatal maturation. We also discuss the role of the Cip/Kip cell cycle inhibitors and Notch signaling in the control of stability of the differentiated state of early postnatal supporting cells. Finally, recent data indicate that some early postnatal mammalian supporting cells retain a latent capacity to divide and transdifferentiate into sensory hair cells. Together, these observations make supporting cells important therapeutic targets for continued efforts to induce hair cell regeneration.
感觉毛细胞的丧失是人类耳聋的主要原因。哺乳动物的耳蜗无法再生其感觉毛细胞。因此，目前因感觉毛细胞丧失导致的耳聋的唯一治疗方法是使用助听器和人工耳蜗等假体。相比之下，在鸟类等非哺乳动物脊椎动物中，毛细胞死亡后会发生毛细胞再生，并导致听力恢复。鸟类的再生之所以成功，是因为围绕毛细胞的支持细胞能够分裂，并随后分化为新的毛细胞。然而，当毛细胞丧失时，哺乳动物的支持细胞通常不会分裂或转分化，因此不会发生再生。为了理解哺乳动物耳蜗毛细胞再生失败的原因，我们需要了解胚胎发育期间和出生后小鼠中细胞分裂控制和毛细胞分化的分子机制。在这篇综述中，我们讨论了胚胎发育和出生后成熟过程中细胞增殖的调控。我们还讨论了Cip/Kip细胞周期抑制剂和Notch信号在控制出生后早期支持细胞分化状态稳定性中的作用。最后，最近的数据表明，一些出生后早期的哺乳动物支持细胞保留了分裂和转分化为感觉毛细胞的潜在能力。总之，这些观察结果使支持细胞成为诱导毛细胞再生持续努力的重要治疗靶点。
