Tai Yilin, Janas Justyna A, Wang Chia-Lin, Van Aelst Linda
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Cell Rep. 2014 Jan 30;6(2):254-63. doi: 10.1016/j.celrep.2013.12.034. Epub 2014 Jan 16.
Chandelier cells (ChCs), typified by their unique axonal morphology, are the most distinct interneurons present in cortical circuits. Via their distinctive axonal terminals, called cartridges, these cells selectively target the axon initial segment of pyramidal cells and control action potential initiation; however, the mechanisms that govern the characteristic ChC axonal structure have remained elusive. Here, by employing an in utero electroporation-based method that enables genetic labeling and manipulation of ChCs in vivo, we identify DOCK7, a member of the DOCK180 family, as a molecule essential for ChC cartridge and bouton development. Furthermore, we present evidence that DOCK7 functions as a cytoplasmic activator of the schizophrenia-associated ErbB4 receptor tyrosine kinase and that DOCK7 modulates ErbB4 activity to control ChC cartridge and bouton development. Thus, our findings define DOCK7 and ErbB4 as key components of a pathway that controls the morphological differentiation of ChCs, with implications for the pathogenesis of schizophrenia.
吊灯细胞（ChCs）以其独特的轴突形态为典型特征，是存在于皮质回路中最独特的中间神经元。通过其独特的轴突终末，即所谓的“弹药筒”，这些细胞选择性地靶向锥体细胞的轴突起始段并控制动作电位的起始；然而，支配ChC特征性轴突结构的机制仍然不清楚。在这里，通过采用基于子宫内电穿孔的方法，该方法能够在体内对ChCs进行基因标记和操作，我们鉴定出DOCK7，它是DOCK180家族的成员，是ChC“弹药筒”和终扣发育所必需的分子。此外，我们提供的证据表明，DOCK7作为精神分裂症相关的ErbB4受体酪氨酸激酶的细胞质激活剂发挥作用，并且DOCK7调节ErbB4活性以控制ChC“弹药筒”和终扣的发育。因此，我们的研究结果将DOCK7和ErbB4定义为控制ChCs形态分化的途径的关键组成部分，这对精神分裂症的发病机制具有重要意义。
