Wan Guoqiang, Gómez-Casati Maria E, Gigliello Angelica R, Liberman M Charles, Corfas Gabriel
F M Kirby Neurobiology Center, Boston Children's Hospital, Boston, United States.
Department of Otology and Laryngology, Harvard Medical School, Boston, United States.
Elife. 2014 Oct 20;3:e03564. doi: 10.7554/eLife.03564.
Neurotrophin-3 (Ntf3) and brain derived neurotrophic factor (Bdnf) are critical for sensory neuron survival and establishment of neuronal projections to sensory epithelia in the embryonic inner ear, but their postnatal functions remain poorly understood. Using cell-specific inducible gene recombination in mice we found that, in the postnatal inner ear, Bbnf and Ntf3 are required for the formation and maintenance of hair cell ribbon synapses in the vestibular and cochlear epithelia, respectively. We also show that supporting cells in these epithelia are the key endogenous source of the neurotrophins. Using a new hair cell CreER(T) line with mosaic expression, we also found that Ntf3's effect on cochlear synaptogenesis is highly localized. Moreover, supporting cell-derived Ntf3, but not Bbnf, promoted recovery of cochlear function and ribbon synapse regeneration after acoustic trauma. These results indicate that glial-derived neurotrophins play critical roles in inner ear synapse density and synaptic regeneration after injury.
神经营养因子-3（Ntf3）和脑源性神经营养因子（Bdnf）对于胚胎内耳感觉神经元的存活以及神经元向感觉上皮的投射建立至关重要，但其出生后的功能仍知之甚少。利用小鼠细胞特异性诱导基因重组，我们发现，在出生后的内耳中，Bbnf和Ntf3分别是前庭和耳蜗上皮中毛细胞带状突触形成和维持所必需的。我们还表明，这些上皮中的支持细胞是神经营养因子的关键内源性来源。利用具有镶嵌表达的新型毛细胞CreER(T)系，我们还发现Ntf3对耳蜗突触发生的影响高度局限。此外，支持细胞衍生的Ntf3而非Bbnf促进了声损伤后耳蜗功能的恢复和带状突触再生。这些结果表明，胶质细胞衍生的神经营养因子在损伤后内耳突触密度和突触再生中起关键作用。
