Neuronal Target Identification Requires AHA-1-Mediated Fine-Tuning of Wnt Signaling in C. elegans

• DOI: 10.1371/journal.pgen.1003618
• Publication Date: 2013-06-27T20:58:10Z
• Authors: Jingyan Zhang; Xia Li; Angela R. Jevince; Liying Guan; Jiaming Wang; David H. Hall; Xun Huang; Mei Ding
• Keywords: 0301 basic medicine; Gap Junctions; Cell Communication; QH426-470; Receptor Tyrosine Kinase-like Orphan Receptors; Synaptic Transmission; DNA-Binding Proteins; 03 medical and health sciences; Electrical Synapses; Receptors, Aryl Hydrocarbon; Interneurons; Genetics; Basic Helix-Loop-Helix Transcription Factors; Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Promoter Regions, Genetic; Mechanoreceptors; Wnt Signaling Pathway; Research Article

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.