The claudin superfamily protein nsy-4 biases lateral signaling to generate left-right asymmetry in C. elegans olfactory neurons.
Early in C. elegans development, signaling between bilaterally symmetric AWC olfactory neurons causes them to express different odorant receptor genes. AWC left-right asymmetry is stochastic: in each animal, either the left or the right neuron randomly becomes AWC(ON), and the other neuron becomes AWC(OFF). Here we show that the nsy-4 gene coordinates the lateral signaling that diversifies AWC(ON) and AWC(OFF) neurons. nsy-4 mutants generate 2 AWC(OFF) neurons, as expected if communication between the AWC neurons is lost, whereas overexpression of nsy-4 results in 2 AWC(ON) neurons. nsy-4 encodes a transmembrane protein related to the gamma subunits of voltage-activated calcium channels and the claudin superfamily; it interacts genetically with calcium channels and antagonizes a calcium-to-MAP kinase cascade in the neuron that becomes AWC(ON). Genetic mosaic analysis indicates that nsy-4 functions both cell-autonomously and nonautonomously in signaling between AWC neurons, providing evidence for lateral signaling and feedback that coordinate asymmetric receptor choice.
Vanhoven
Miri K
MK
Department of Anatomy and Department of Biochemistry and Biophysics, The University of California, San Francisco, San Francisco, California 94143, USA.
Bauer Huang
Sarah L
SL
Albin
Stephanie D
SD
Bargmann
Cornelia I
CI
D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D062445:Claudin-1; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D005810:Multigene Family; D009154:Mutation; D018034:Olfactory Receptor Neurons / Q000254:growth & development*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D019108:Tight Junctions / Q000235:genetics / Q000502:physiology*; D019076:Transgenes / Q000502:physiology*
D029742:Caenorhabditis elegans Proteins; D062445:Claudin-1; D008565:Membrane Proteins