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C. elegans can sense hundreds of odors, discriminate among them, and generate different behaviors in response to different odors. The left and right amphid wing C (AWC) neurons of the C. elegans olfactory system are bilaterally symmetric with regard to their morphological and anatomical features and develop asymmetry at the molecular and functional level. The candidate odorant receptor gene str-2 is randomly expressed in only one of the two AWC neurons. The AWC neurons are distinguished by whether they express the candidate odorant receptor gene str-2::GFP as AWCON and AWCOFF (figure 1).
Our research has been focusing on signaling pathways that create AWC neuronal asymmetry and has revealed an important role of a transient, embryonic gap junction neural network and synaptic signaling molecules in neuronal maturation. AWC neuronal asymmetry is determined in a stochastic manner through the modulation of calcium signaling by NSY-5 gap junctions and synapse-mediated cell-cell communication across the midline (figure 2). AWC asymmetry seems to be evolutionarily advantageous since it allows the worm to sense multiple odors using a limited number of olfactory sensory neurons.
We are extending these discoveries in several directions to further define the logic of cell-cell communication and signaling events that specify left-right neuronal asymmetry. Our current research is focused on the following questions:
The establishment of C. elegans left-right AWC neuronal asymmetry by transient NSY-5 gap junctions and the genetically downstream calcium-regulated signaling pathway provides an attractive system to elucidate the molecular mechanisms of cell-cell communication in brain asymmetry. Studies in C. elegans have led to the discovery of many important biological processes that are conserved from worms to humans including axon guidance, programmed cell death, RNA interference and miRNA-guided post-transcriptional gene regulation. Our study of left-right asymmetric neuronal specification in C. elegans will shed light on the mechanisms of human brain asymmetry and could lead to the development of therapeutic strategies for treating laterality-based neurological disorders.
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Left-right neuronal asymmetry in C. elegans. The left and right AWC olfactory neurons in the head represent distinct cell types. The candidate odorant receptor str-2::GFP (false-colored green) is expressed in only one of the two AWC neurons. AWCON, str-2-expressing AWC cell; AWCOFF, non-str-2-expressing cell.
NSY-5 gap junction neural network specifies left-right AWC neuronal asymmetry. The promoter of NSY-5 innexin gap junction gene drives green fluorescent protein (GFP) expression in a cell network, which consists of many sensory neurons and interneurons (false-colored green). Individual neighboring neurons in the gap junction network communicate to help AWC neurons fine-tune the signaling for the establishment of precise asymmetry.
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