Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
Proc Natl Acad Sci U S A. 2013 Aug 27;110(35):14456-61. doi: 10.1073/pnas.1307376110. Epub 2013 Aug 12.
In the cochlear nucleus (CN), the first central relay of the auditory pathway, the survival of neurons during the first weeks after birth depends on afferent innervation from the cochlea. Although input-dependent neuron survival has been extensively studied in the CN, neurogenesis has not been evaluated as a possible mechanism of postnatal plasticity. Here we show that new neurons are born in the CN during the critical period of postnatal plasticity. Coincidently, we found a population of neural progenitor cells that are controlled by a complex interplay of Wnt, Notch, and TGFβ/BMP signaling, in which low levels of TGFβ/BMP signaling are permissive for progenitor proliferation that is promoted by Wnt and Notch activation. We further show that cells with activated Wnt signaling reside in the CN and that these cells have high propensity for neurosphere formation. Cochlear ablation resulted in diminishment of progenitors and Wnt/β-catenin-active cells, suggesting that the neonatal CN maintains an afferent innervation-dependent population of progenitor cells that display active canonical Wnt signaling.
在耳蜗核（CN）中，听觉通路的第一个中枢中继，神经元在出生后的头几周的存活取决于来自耳蜗的传入神经支配。尽管已经广泛研究了输入依赖性神经元存活，但尚未将神经发生评估为产后可塑性的可能机制。在这里，我们显示在产后可塑性的关键时期，CN 中会产生新的神经元。巧合的是，我们发现了一群神经祖细胞，它们受到 Wnt、Notch 和 TGFβ/BMP 信号的复杂相互作用的控制，其中低水平的 TGFβ/BMP 信号允许由 Wnt 和 Notch 激活促进的祖细胞增殖。我们进一步表明，具有激活的 Wnt 信号的细胞存在于 CN 中，并且这些细胞具有形成神经球的高倾向。耳蜗消融导致祖细胞和 Wnt/β-catenin-活性细胞减少，这表明新生的 CN 维持了具有活跃经典 Wnt 信号的、依赖传入神经支配的祖细胞群体。
