在听觉系统中，内耳在柯蒂氏器（Organ of Corti）中将声波转换成电信号，柯蒂氏器上布满了15000至20000个毛发状细胞。这些细胞对振动作出反应，产生电刺激通过神经传给大脑。这是一个脆弱的系统——高分贝的声音会损伤毛发状细胞，机体老化也会使它们衰竭，从而导致听力损失。科学家推测，可以通过替换这些毛发细胞来恢复部分听力功能。之前的研究鉴别出一种名为Atoh1的蛋白，它可以触发毛发细胞的生长。但是这些人工形成的细胞是否与天然细胞具有一样的功能并不清楚。
Nature，doi:10.1038/nature07265，Samuel P. Gubbels，John V. Brigande
Functional auditory hair cells produced in the mammalian cochlea by in utero gene transfer
Samuel P. Gubbels1,4,5, David W. Woessner1,4,5, John C. Mitchell2, Anthony J. Ricci3 & John V. Brigande1
Sensory hair cells in the mammalian cochlea convert mechanical stimuli into electrical impulses that subserve audition1, 2. Loss of hair cells and their innervating neurons is the most frequent cause of hearing impairment3. Atonal homologue 1 (encoded by Atoh1, also known as Math1) is a basic helix–loop–helix transcription factor required for hair-cell development4, 5, 6, and its misexpression in vitro 7, 8 and in vivo 9, 10 generates hair-cell-like cells. Atoh1-based gene therapy to ameliorate auditory10 and vestibular11 dysfunction has been proposed. However, the biophysical properties of putative hair cells induced by Atoh1 misexpression have not been characterized. Here we show that in utero gene transfer of Atoh1 produces functional supernumerary hair cells in the mouse cochlea. The induced hair cells display stereociliary bundles, attract neuronal processes and express the ribbon synapse marker carboxy-terminal binding protein 2 (refs 12,13). Moreover, the hair cells are capable of mechanoelectrical transduction1, 2 and show basolateral conductances with age-appropriate specializations. Our results demonstrate that manipulation of cell fate by transcription factor misexpression produces functional sensory cells in the postnatal mammalian cochlea. We expect that our in utero gene transfer paradigm will enable the design and validation of gene therapies to ameliorate hearing loss in mouse models of human deafness14, 15.
