Department of Neuroscience, University of Virginia School of Medicine, 409 Lane Rd, Charlottesville, VA 22908, USA.
J Assoc Res Otolaryngol. 2012 Oct;13(5):609-27. doi: 10.1007/s10162-012-0337-0. Epub 2012 Jul 3.
Many non-mammalian vertebrates produce hair cells throughout life and recover from hearing and balance deficits through regeneration. In contrast, embryonic production of hair cells declines sharply in mammals where deficits from hair cell losses are typically permanent. Hair cell density estimates recently suggested that the vestibular organs of mice continue to add hair cells after birth, so we undertook comprehensive counting in murine utricles at different ages. The counts show that 51% of the hair cells in adults arise during the 2 weeks after birth. Immature hair cells are most common near the neonatal macula's peripheral edge and striola, where anti-Ki-67 labels cycling nuclei in zones that appear to contain niches for supporting-cell-like stem cells. In vivo lineage tracing in a novel reporter mouse where tamoxifen-inducible supporting cell-specific Cre expression switched tdTomato fluorescence to eGFP fluorescence showed that proteolipid-protein-1-expressing supporting cells are an important source of the new hair cells. To assess the contributions of postnatal cell divisions, we gave mice an injection of BrdU or EdU on the day of birth. The labels were restricted to supporting cells 1 day later, but by 12 days, 31% of the labeled nuclei were in myosin-VIIA-positive hair cells. Thus, hair cell populations in neonatal mouse utricles grow appreciably through two processes: the progressive differentiation of cells generated before birth and the differentiation of new cells arising from divisions of progenitors that progress through S phase soon after birth. Subsequent declines in these processes coincide with maturational changes that appear unique to mammalian supporting cells.
许多非哺乳动物脊椎动物在一生中产生毛细胞,并通过再生从听力和平衡缺陷中恢复。相比之下,哺乳动物胚胎中毛细胞的产生急剧下降,毛细胞的损失导致的缺陷通常是永久性的。最近的毛细胞密度估计表明,小鼠的前庭器官在出生后仍会产生毛细胞,因此我们在不同年龄的小鼠前庭中进行了全面计数。这些计数表明,成年小鼠的毛细胞有 51%是在出生后两周内产生的。未成熟的毛细胞在靠近新生儿嵴的周边边缘和条纹处最为常见,抗 Ki-67 标记了处于似乎包含支持细胞样干细胞龛的区域中的有丝分裂核。在一种新型报告小鼠中进行的体内谱系追踪实验中,tamoxifen 诱导的支持细胞特异性 Cre 表达将 tdTomato 荧光转换为 eGFP 荧光,结果表明表达蛋白脂质蛋白-1 的支持细胞是新毛细胞的重要来源。为了评估出生后细胞分裂的贡献,我们在出生当天给小鼠注射 BrdU 或 EdU。标记物仅在 1 天后局限于支持细胞,但在 12 天时,31%的标记核位于肌球蛋白-VIIA 阳性毛细胞中。因此,新生小鼠前庭中的毛细胞群体通过两种过程显著增长:出生前产生的细胞的逐步分化,以及由出生后很快通过 S 期的祖细胞分裂产生的新细胞的分化。随后这些过程的下降与似乎是哺乳动物支持细胞特有的成熟变化同时发生。