In order to survive, an organism must be able to receive, integrate, and respond to sensory stimuli. However, the cellular basis of sensory perception and response is difficult to study in complex animals such as humans, and is therefore poorly understood. The nematode Caenorhabditis elegans is a relatively simple organism yet displays many distinct behaviors, making it an ideal system to understand the relationship between gene function, cell shape, cell physiology, and behavioral output. Much of the thermosensory and chemosensory information that the nematode receives from its sensory neurons is processed via a pair of interneurons called AIYL and AIYR. In wildtype animals, the AIY cell bodies lie just posterior to the pharynx, and extend an anterior process that contacts its contralateral partner at the base of the nerve ring. The AIYL and R processes then diverge and extend around the nerve ring, ultimately making contact again on the dorsal side of the animal via a gap junction. We previously showed that the Eph receptor tyrosine kinase
vab-1 is required for AIY cell body placement and ventral AIYL/R contact. Conversely, the ephrin
efn-4 is required for dorsal AIYL/R connectivity. We have extended these studies and show that the AIYL/R ventral contact is mediated via the ephrin gene
efn-1. In addition, we show that this connectivity requires both
vab-1 kinase activity and also a non-kinase dependent
vab-1 function. We are currently performing tissue specific rescue experiments to understand whether
efn-1 functions cell autonomously in AIY development. To integrate AIYL/R morphology and function with behavior, we are using WormLab software to image and analyze EphR/ephrin mutants both on and off food. Wildtype animals search for food using long "runs" interspersed with reversals and ~170-degree "omega" turns. We find that
vab-1 mutants lack the ability to perform straight runs, although they can perform omega turns normally. Instead, they display a strong circling locomotion, both on and off food. When EphR/ephrin pathway mutants are conditioned in a 150mM NaCl environment with food, then assayed on a food-free NaCl gradient,
vab-1,
efn-1 and
efn-4 mutants all display normal chemotaxis towards a point NaCl source, suggesting no overt defects with NaCl conditioning and chemotaxis. We are currently investigating neuromuscular junction morphology in EphR and ephrin mutants to see if this correlates with dorsal versus ventral locomotion bias.