title: Intercellular calcium signaling in a gap junction-coupled cell network establishes asymmetric neuronal fates in C. elegans.
abstract: The C. elegans left and right AWC olfactory neurons specify asymmetric subtypes, one default AWC(OFF) and one induced AWC(ON), through a stochastic, coordinated cell signaling event. Intercellular communication between AWCs and non-AWC neurons via a NSY-5 gap junction network coordinates AWC asymmetry. However, the nature of intercellular signaling across the network and how individual non-AWC cells in the network influence AWC asymmetry is not known. Here, we demonstrate that intercellular calcium signaling through the NSY-5 gap junction neural network coordinates a precise 1AWC(ON)/1AWC(OFF) decision. We show that NSY-5 gap junctions in C. elegans cells mediate small molecule passage. We expressed vertebrate calcium-buffer proteins in groups of cells in the network to reduce intracellular calcium levels, thereby disrupting intercellular communication. We find that calcium in non-AWC cells of the network promotes the AWC(ON) fate, in contrast to the autonomous role of calcium in AWCs to promote the AWC(OFF) fate. In addition, calcium in specific non-AWCs promotes AWC(ON) side biases through NSY-5 gap junctions. Our results suggest a novel model in which calcium has dual roles within the NSY-5 network: autonomously promoting AWC(OFF) and non-autonomously promoting AWC(ON).
authors.affiliation: Division of Developmental Biology, Children's Hospital Medical Center Research Foundation, 240 Albert Sabin Way, Cincinnati, OH 45229,  USA.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Schumacher
authors.forename: Yi-Wen
authors.initials: YW
authors.lastname: Hsieh
authors.forename: Shiuhwei
authors.initials: S
authors.lastname: Chen
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Pirri
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Alkema
authors.forename: Wen-Hong
authors.initials: WH
authors.lastname: Li
authors.forename: Chieh
authors.initials: C
authors.lastname: Chang
authors.forename: Chiou-Fen
authors.initials: CF
authors.lastname: Chuang
mesh_terms: D000818:Animals; D001692:Biological Transport; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D064026:Calbindins; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D002450:Cell Communication; D002478:Cells, Cultured; D017630:Connexins / Q000378:metabolism*; D017629:Gap Junctions / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D007473:Ion Channels / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D009833:Olfactory Pathways; D018034:Olfactory Receptor Neurons / Q000166:cytology / Q000378:metabolism*; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D029742:Caenorhabditis elegans Proteins; D064026:Calbindins; D017630:Connexins; D007473:Ion Channels; D008565:Membrane Proteins; D064030:S100 Calcium Binding Protein G; C521128:inx-19 protein, C elegans; C093204:unc-2 protein, C elegans; D002118:Calcium