title: Neuronal target identification requires AHA-1-mediated fine-tuning of Wnt signaling in C. elegans.
abstract: 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.
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Jingyan
authors.initials: J
authors.lastname: Zhang
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.forename: Angela R
authors.initials: AR
authors.lastname: Jevince
authors.forename: Liying
authors.initials: L
authors.lastname: Guan
authors.forename: Jiaming
authors.initials: J
authors.lastname: Wang
authors.forename: David H
authors.initials: DH
authors.lastname: Hall
authors.forename: Xun
authors.initials: X
authors.lastname: Huang
authors.forename: Mei
authors.initials: M
authors.lastname: Ding
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D002450:Cell Communication / Q000235:genetics / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics; D054351:Electrical Synapses / Q000235:genetics / Q000502:physiology; D017629:Gap Junctions / Q000235:genetics / Q000502:physiology; D007395:Interneurons / Q000502:physiology; D008465:Mechanoreceptors / Q000502:physiology; D011401:Promoter Regions, Genetic; D057050:Receptor Tyrosine Kinase-like Orphan Receptors / Q000235:genetics*; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics*; D009435:Synaptic Transmission / Q000235:genetics* / Q000502:physiology; D060449:Wnt Signaling Pathway / Q000235:genetics*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D057050:Receptor Tyrosine Kinase-like Orphan Receptors; D018336:Receptors, Aryl Hydrocarbon; C583320:AHA-1 protein, C elegans; C484723:ahr-1 protein, C elegans; C526267:CAM-1 protein, C elegans