電突觸介導的信號傳遞是神經(jīng)細胞相互交流的一種基本方式,，是腦感知、學習和記憶的基礎,，是神經(jīng)網(wǎng)絡構成的重要環(huán)節(jié),。然而，神經(jīng)細胞是如何識別其正確目標神經(jīng)并形成電突觸的分子機理并不清楚,。
中國科學院遺傳與發(fā)育生物學研究所丁梅實驗室以秀麗隱桿線蟲為模式,，發(fā)現(xiàn)BDU中間神經(jīng)元和PLM機械感受神經(jīng)元特異性地接觸在一起，電鏡及化學標記實驗表明這二者通過電突觸連接,。遺傳學篩選發(fā)現(xiàn)PAS-bHLH轉(zhuǎn)錄因子家族的兩個成員,，AHA-1和AHR-1，對于BDU-PLM連接的形成至關重要,。系統(tǒng)的細胞自主性拯救實驗結果證明：AHA-1和AHR-1,，同時在BDU和PLM神經(jīng)元中發(fā)揮功能，從而促進神經(jīng)元的連接。AHA-1可結合cam-1的啟動子區(qū)域,，增強 cam-1的轉(zhuǎn)錄,，通過拮抗Wnt信號調(diào)控BDU神經(jīng)元和PLM神經(jīng)元特異連接的形成。該研究揭示了局部Wnt信號通路微調(diào)影響互為靶細胞的電突觸形成細胞的目標識別過程,，豐富了人們對Wnt信號通路調(diào)控機理的認識,，并為活體研究電突觸提供了新的切入點。
此研究結果在線發(fā)表于6月27日的PLoS Genetics雜志上,，丁梅課題組博士生張景彥為該論文的第一作者,，黃勛和丁梅研究員是本文章的共同通訊作者。
該研究得到了國家自然科學基金委,、科技部和中科院的資助,。（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.
