电突触介导的信号传递是神经细胞相互交流的一种基本方式，是脑感知、学习和记忆的基础，是神经网络构成的重要环节。然而，神经细胞是如何识别其正确目标神经并形成电突触的分子机理并不清楚。
中国科学院遗传与发育生物学研究所丁梅实验室以秀丽隐杆线虫为模式，发现BDU中间神经元和PLM机械感受神经元特异性地接触在一起，电镜及化学标记实验表明这二者通过电突触连接。遗传学筛选发现PAS-bHLH转录因子家族的两个成员，AHA-1和AHR-1，对于BDU-PLM连接的形成至关重要。系统的细胞自主性拯救实验结果证明：AHA-1和AHR-1，同时在BDU和PLM神经元中发挥功能，从而促进神经元的连接。AHA-1可结合cam-1的启动子区域，增强 cam-1的转录，通过拮抗Wnt信号调控BDU神经元和PLM神经元特异连接的形成。该研究揭示了局部Wnt信号通路微调影响互为靶细胞的电突触形成细胞的目标识别过程，丰富了人们对Wnt信号通路调控机理的认识，并为活体研究电突触提供了新的切入点。
此研究结果在线发表于6月27日的PLoS Genetics杂志上，丁梅课题组博士生张景彦为该论文的第一作者，黄勋和丁梅研究员是本文章的共同通讯作者。
该研究得到了国家自然科学基金委、科技部和中科院的资助。（生物谷Bioon.com）
doi:10.1371/journal.pgen.1003618
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Neuronal Target Identification Requires AHA-1-Mediated Fine-Tuning of Wnt Signaling in C. elegans
Zhang J, Li X, Jevince AR, Guan L, Wang J, et al.
Electrical synaptic transmission through gap junctions is a vital mode of intercellular communication in the nervous system. The mechanism by which reciprocal target cells find each other during the formation of gap junctions, however, is poorly understood. Here we show that gap junctions are formed between BDU interneurons and PLM mechanoreceptors in C. elegans and the connectivity of BDU with PLM is influenced by Wnt signaling. We further identified two PAS-bHLH family transcription factors, AHA-1 and AHR-1, which function cell-autonomously within BDU and PLM to facilitate the target identification process. aha-1 and ahr-1 act genetically upstream of cam-1. CAM-1, a membrane-bound receptor tyrosine kinase, is present on both BDU and PLM cells and likely serves as a Wnt antagonist. By binding to a cis-regulatory element in the cam-1 promoter, AHA-1 enhances cam-1 transcription. Our study reveals a Wnt-dependent fine-tuning mechanism that is crucial for mutual target cell identification during the formation of gap junction connections.
