The role of EphR/ephrin signaling in a food-seeking sensorimotor neural circuit
Abstract (300 words maximum)
In order for the nervous system to develop accurately, specific guidance molecules are required in order for neurons to create contact with adjacent neurons at their cell-surface receptors. Eph Receptor tyrosine kinases (EphRs) and their ephrin ligands are crucial for many aspects of vertebrate CNS development, and mutations in these genes lead to a variety of neurodevelopmental defects. Studying these molecular aspects of these proteins in mice is difficult due to overlap in EphR and ephrin expression pattern and function. However, the nematode C. elegans contains only a single EphR and just 4 ephrin ligands making it a simple system for investigating EphR/ephrin function.
Previous work from the Hudson lab showed that mutations in the EphR/ephrin pathway led to defects in food seeking forward locomotion. Using GFP-reporter genes, we identified morphological defects in AIY interneuron development. The AIY interneurons are part of a circuit that processes information from amphid chemosensory and thermosensory neurons to the command motor neurons, and are crucial for controlling attractive and aversive behaviors.
To better understand the role of EphR/ephrin function in the sensorimotor circuit, we performed tissue-specific rescue experiments. We find that driving ephrin-1 expression from a pan-neural promoter is sufficient to rescue ephrin-1 dependent food-seeking behavioral defects. However, this did not rescue the morphology of AIY interneurons, suggesting that defects in either the sensory neurons or the motor neurons underpin the behavioral phenotype observed. Work is on going to understand what role the EphR/ephrin genes play in sensory neuron development, and motor neuron development.
Academic department under which the project should be listed
CSM - Molecular and Cellular Biology
Primary Investigator (PI) Name
Dr. Martin Hudson
The role of EphR/ephrin signaling in a food-seeking sensorimotor neural circuit
In order for the nervous system to develop accurately, specific guidance molecules are required in order for neurons to create contact with adjacent neurons at their cell-surface receptors. Eph Receptor tyrosine kinases (EphRs) and their ephrin ligands are crucial for many aspects of vertebrate CNS development, and mutations in these genes lead to a variety of neurodevelopmental defects. Studying these molecular aspects of these proteins in mice is difficult due to overlap in EphR and ephrin expression pattern and function. However, the nematode C. elegans contains only a single EphR and just 4 ephrin ligands making it a simple system for investigating EphR/ephrin function.
Previous work from the Hudson lab showed that mutations in the EphR/ephrin pathway led to defects in food seeking forward locomotion. Using GFP-reporter genes, we identified morphological defects in AIY interneuron development. The AIY interneurons are part of a circuit that processes information from amphid chemosensory and thermosensory neurons to the command motor neurons, and are crucial for controlling attractive and aversive behaviors.
To better understand the role of EphR/ephrin function in the sensorimotor circuit, we performed tissue-specific rescue experiments. We find that driving ephrin-1 expression from a pan-neural promoter is sufficient to rescue ephrin-1 dependent food-seeking behavioral defects. However, this did not rescue the morphology of AIY interneurons, suggesting that defects in either the sensory neurons or the motor neurons underpin the behavioral phenotype observed. Work is on going to understand what role the EphR/ephrin genes play in sensory neuron development, and motor neuron development.