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Neuron. 2006 Aug 3;51(3):291-302.

The claudin superfamily protein nsy-4 biases lateral signaling to generate left-right asymmetry in C. elegans olfactory neurons.

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Department of Anatomy and Department of Biochemistry and Biophysics, The University of California, San Francisco, San Francisco, California 94143, USA.


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.

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