F. M. Kirby Neurobiology Center, Children's Hospital Boston, Boston, MA 02115, USA.
Proc Natl Acad Sci U S A. 2010 Sep 28;107(39):17005-10. doi: 10.1073/pnas.1008938107. Epub 2010 Sep 13.
Recent studies indicate that molecules released by glia can induce synapse formation. However, what induces glia to produce such signals, their identity, and their in vivo relevance remain poorly understood. Here we demonstrate that supporting cells of the vestibular organ--cells that have many characteristics of glia--promote synapse formation only when induced by neuron-derived signals. Furthermore, we identify BDNF as the synaptogenic signal produced by these nonneuronal cells. Mice in which erbB signaling has been eliminated in supporting cells have vestibular dysfunction caused by failure of synapse formation between hair cells and sensory neurons. This phenotype correlates with reduced BDNF expression in supporting cells and is rescued by reexpression of BDNF in these cells. Furthermore, knockdown of BDNF expression in supporting cells postnatally phenocopies the loss of erbB signaling. These results indicate that vestibular supporting cells contribute in vivo to vestibular synapse formation and that this is mediated by reciprocal signals between sensory neurons and supporting cells involving erbB receptors and BDNF.
最近的研究表明,神经胶质细胞释放的分子可以诱导突触形成。然而,是什么诱导神经胶质细胞产生这种信号,它们的身份以及它们在体内的相关性仍知之甚少。在这里,我们证明前庭器官的支持细胞——具有许多神经胶质细胞特征的细胞——只有在受到神经元衍生信号诱导时才促进突触形成。此外,我们确定 BDNF 是这些非神经元细胞产生的促突触形成信号。在支持细胞中消除 erbB 信号的小鼠由于毛细胞和感觉神经元之间的突触形成失败而出现前庭功能障碍。这种表型与支持细胞中 BDNF 表达减少相关,并且可以通过在这些细胞中重新表达 BDNF 来挽救。此外,支持细胞中 BDNF 表达的敲低在出生后模拟了 erbB 信号的缺失。这些结果表明,前庭支持细胞在体内有助于前庭突触的形成,并且这是由涉及 erbB 受体和 BDNF 的感觉神经元和支持细胞之间的相互信号介导的。