Chemosensation allows animals to evaluate their environment, detect food, other animals, and dangerous toxins while responding with appropriate behaviors essential to the animal''s survival. A robust chemosensory system can be generated even from a seemingly simple nervous system, such as that of C. elegans, which can detect and respond to a vast number of chemical cues. One important, but poorly understood, strategy used by C. elegans is to "lateralize" the function of some of its sensory neurons, such as the ASE neurons, thus increasing the discriminatory power of a system comprised of relatively few elements. We have found that the ASE neurons respond to several salt cues and these responses are asymmetric in terms of whether the left or the right ASE neuron responds to a specific salt cue (Ortiz et al., submitted). Previous work in our lab has furthermore identified a number of guanylyl cyclase genes as having a role in the chemotaxis asymmetry of ASE (Ortiz et al., submitted). Mutant analysis has revealed that individual gcy genes are specifically required for sensing particular ions. Such specificity could be conferred through either the protein''s receptor family ligand-binding region (RFLBR) in its extracellular domain or by the protein''s guanylyl cyclase (GC) domain in its intracellular region. We seek to identify the molecular mechanisms by which these asymmetrically expressed receptor type guanylyl cyclases confer the specificity that underlies this lateralization. In order to test these predictions, intra- or extra-cellular domains of individual GCY proteins were swapped, chimeric proteins were introduced into mutant background animals in a cell-specific manner, and then rescue of chemotaxis defects were tested. The individual GCY protein domains that confer the cellular specificity of ASE neurons, which enables them to mediate responses only to particular cues are identified by evaluating assay output. Results from such experiments allow for the characterization of the domain(s) essential for specificity. By identifying these molecular mechanisms, key predictions of the role that these proteins play in ASE neurons, putatively functioning either as chemoreceptors or, alternatively, as signal transducers, can begin to be tested. We will pursue further strategies for elucidating these molecular mechanisms as part of an overall effort in exploring the relationship between individual genes, their patterns of expression in specific cellular contexts, and the chemosensory behaviors exhibited by C. elegans in response to salt cues found in its environment.