Analysis of genetic and functional asymmetry in the gustatory system of Caenorhabditis elegans

Animal survival requires that organisms are able to continually assess ambient conditions and generate appropriate behavioral responses. The detection of relevant chemical compounds is particularly important as chemosensory cues provide critical information that, among other things, allows animals to identify both nutritious food sources and potentially toxic substances that are to be avoided. Although the detection of salts is particularly important to maintain fluid and electrolyte homeostasis, among the five major taste modalities, the molecular mechanisms of salt taste are the most poorly understood.The nematode Caenorhabditis elegans provides a powerful model system in which to study both the cellular and molecular underpinnings of behavior in general, but especially of chemosensation. Despite possessing a simple nervous system of only 302 neurons, it is capable of detecting a wide array of chemical compounds that elicit either attraction or avoidance behavior. Worms are attracted to low salt concentrations and repelled by very high salt concentrations. Higher level processing is also present, allowing worms to discriminate between multiple chemical cues and integrate relevant information from multiple sensory stimuli into memories that lead to adaptive behavioral responses. Powerful genetic and imaging techniques in this model system provide the opportunity to examine how this morphologically well described, compact nervous system detects, encodes, and processes sensory stimuli.In this study I focus on a specific class of C. elegans gustatory neurons, ASE, and some of the mechanisms these cells recruit to detect multiple salt taste cues. Although most classes of sensory neurons are thought to be bilaterally symmetric across the left/right axis, ASE displays both genetic and functional asymmetry. Several receptor-type guanylyl cyclases (rGCs) of the gcy gene family were known to be asymmetrically expressed in ASE in a manner that correlated with asymmetric salt ion sensitivity. To both find more examples of lateralized gene expression in ASE and to investigate the role of the gcy genes in salt taste, I performed a genomewide analysis of all guanylyl cyclases, which revealed 27 genes encoding rGCs and seven genes encoding soluble guanylate cyclases (sGCs). I then used green fluorescent protein (gfp) reporters to study the cellular expression patterns of uncharacterized rGCs, uncovering a striking enrichment of these genes in chemosensory neurons. ASE alone harbors 11 out of 27 rGCs, most commonly in a left/right asymmetric manner. Having established that putative gcy chemoreceptors are concentrated in ASE in an asymmetric fashion, I sought to find more examples of lateralized gustatory responsiveness in ASE and to characterize the chemotaxis behavior of several gcy mutant strains. I confirmed that ASE responds to other inorganic salt taste cues in an asymmetric manner and that this requires the function of asymmetrically expressed gcy genes. The functional importance of distinct ASE cell fates across the left/right axis is demonstrated by the emergence of a novel behavioral response to a subset of taste cues when ASE cell fate is "symmetrized". Overall these results suggest that rGCs are critical mediators of salt taste signaling in C. elegans and that asymmetric gene expression underlies functional laterality that acts to broaden chemosensory responsiveness in a very compact gustatory system.