Research Synopsis

 

The overall goal of out research is to investigate how the nervous system senses and integrates environmental cues to drive critically important behavioral programs using the model organisms the nematode C. elegans. Specifically, out lab is mainly studying two C. elegans behaviors including pheromone-mediated behavioral plasticity and proprioception. Since neuronal and molecular pathways in C. elegans are highly conserved, results from this work are expected to provide insights into related signaling mechanisms in higher organisms.

 

 

1.      Plasticity in pheromone-mediated avoidance behavior

Our lab is interested in investigating the circuit mechanisms underlying behavioral plasticity and identifying the molecular and neuronal mechanisms required for flexible behaviors even in isogenic population. In previous work (Jang, Kim et al, Neuron 2012) we together with Piali lab and Cori lab identified a novel circuit mediating avoidance of the ascr#3 pheromone in which the nociceptive ADL chemosensory neurons detect it and mediate avoidance behaviors via their chemical synapses. Our lab further showed that early ascr#3 experience enhances repulsion to ascr#3 of adult hermaphrodites via the functional modification of the ascr#3 avoidance circuit, indicating that ascr#3  experienced animals form a long-lasting memory for ascr#3 (Hong, Ryu et al., Current Biology 2017). To our knowledge, this would be the first example for pheromone sensory imprinting.  Moreover, we also showed that ascr#3 avoidance behavior is further modulated by feeding state via insulin signaling pathway (Ryu et al., EMBO Journal 2018). To our knowledge, this is the first example of regulation of pheromone sensory behavior by feeding state in any system. We continue to explore additional genes and other conditions that modulate ascr#3 avoidance behaviors.

 

1. Cheon Y., Hwang H., and Kim K. (2020) Plasticity of pheromone-mediated avoidance behavior in C. elegans. Invited Review. Journal of Neurogenetics. DOI: 10.1080/01677063.2020.1802723 (Invited review)

2. Ryu, L., Cheon Y., Huh, Y., Pyo, S., Chinta, S., Choi, H., Butcher, R., and Kim K. (2018) Feeding state influences pheromone-mediated avoidance behavior via the insulin signaling pathway in C. elegans. The EMBO Journal. 37 e98402.

3. Hong, M.*, Ryu L.*, Ow, M., Kim, J., Je, A., Chinta, S., Huh, Y., Lee, K., Butcher, R., Choi, H., Sengupta, P., Hall, S., and Kim K. (2017) Early pheromone experience modifies a synaptic activity to influence adult pheromone-responses of C. elegans. Current Biology. 27:3168-3177.

4. Jang, H.*, Kim K.*#, Neal, S., Macosko E., Kim, D., Butcher, R., Zeiger, D., Bargmann, C.#, and Sengupta, P.# (2012) Neuromodulatory state and sex specify alternative behaviors through antagonistic synaptic pathways in C. elegans. Neuron. 75:585-592. (*equal contribution; #co-corresponding).

 

 

2.      Proprioception

Our lab is also interested in neuronal basis of proprioception. Animal locomotion is mediated by a highly coordinated sensorimotor feedback system referred to collectively as proprioception. Specialized proprioceptive neurons sense body and limb movements via stretch-sensitive proprioceptive receptors. These signals are subsequently integrated and processed in the brain to coordinate motor activities including muscle contractions. Defects in the proprioception-mediated coordination of locomotion result in uncontrolled and inefficient movements such as ataxic gait. However, little is known about the molecular mechanisms underlying proprioception, and how proprioception modulates sensorimotor coordination. Of particular interest is the finding of the cells and stretch-sensitive molecules that mediate proprioception. We firstly identified a gene which is necessary and sufficient to specifiy a fate of putative proprioceptive neruons (Kim and Yeon et al., PLoS Genetics 2015). We then identified a set of bona fideproprioceptive neurons and two proprioceptors in C. elegans (Yeon and Kim et al., PLoS Biology 2018).  In addition, we characterize an evolutionarily conserved mechanosensitive PIEZO channels of which functions have been shown to be involved in proprioception of mammalian. We found that C. elegans PIEZO channel pezo-1is required for intestinal peristalsis in addition to a putative role of proprioception  (Yeon et al., in prep). Moreover, we identified a role of FMRFamide-related neuropeptide FLP-12 and its cognate FRPR-8 in proprioception (Kim et al., in prep). Our results will elucidate mechanisms of proprioceptive feedback system and will contribute to understand brain function in movement.

 

1. Yeon J.*, Park Y.*, Kim D., Huh W., Hwang H., Jun S., Xiaofei B., Golden A., Lee K., and Kim K. Piezo channel PEZO-1 regulates intestinal motility in C. elegans. In preparation.

2. Kim D., Park C.,  Moon K., Li C., Suh B., and Kim K. FMRFamide-related neuropeptide FLP-12 regulates head locomotion of C. elegans.  In preparation.

3. Yeon, J.*, Kim, J.*, Kim, D., Kim, H., Kim, J, Du, E., Kang, K., Lim, H., Moon, D., and Kim K. (2018) A sensory-motor neuron type mediates proprioceptive coordination of locomotion via two TRPC channels. PLoS Biology. 16(6):e2004929.

4. Kim J.*, Yeon J.*, Choi S., Huh Y., Zhi F., Park S., Kim M., Ryoo Z., Kang K., Kweon H., Jeon W., Li C.# and Kim K.# (2015) The evolutionary conserved LIM homeodomain protein LIM-4/LHX6 specifies the terminal identity of a cholinergic C. elegans sensory/inter/motor neuron-type. PLoS Genetics. 11(8):e1005480 (#co-corresponding).

 

 

3.      Developmental plasticity in pheromone-mediated dauer foramtion

C. elegans exhibits polyphenic development depending upon environment signals; early L1/L2 larvae of C. elegans senses and processes environmental signals including food, temperature and levels of dauer-inducing pheromones as a population density indicator and decides whether animals undergo normal reproductive development into the L3 larval stage in favorable environmental conditions or enter diapause, an alternative L3 larvae referred to as dauer. We took advantage of an ongoing collaboration with Dr. Piali Sengupta, to follow up a project on dauer formation and identified crucial genes including cmk-1 CaMK and crh-1 CREB to mediated dauer formation (Park et al., in prep, Neals et al.,  eLIFE 2015).

 

1. Park J., Oh H., Kim D, Chun Y., Park Y., Neal S., Dar A., Butcher A., Sengupta P., Kim D., and Kim K. CREB mediates a developmental plasticity via the TGF-β signaling in C. elegans. Under revision.

2. Park, J., Choi, W., Dar, A., Butcher, R., and Kim K. (2019) Neuropeptide signaling regulates pheromone-mediated gene expression of a chemoreceptor gene in C. elegans. Molecules and Cells. 42(1):28-35

3. Neal, S., Park, J., DiTirro, D., Yoon, J., Shibuya, M., Choi, W., Schroeder, F.C., Butcher, R.A., Kim K.#, and Sengupta, P.# (2016) A Forward Genetic Screen for Molecules Involved in Pheromone-Induced Dauer Formation in Caenorhabditis elegans. G3. g3.115.026450. 

4. Neal S., Takeishi A., O’Donnell M., Park J., Hong M., Butcher R., Kim K.#, and Sengupta P.# (2015) Feeding state-dependent regulation of developmental plasticity via CaMKI and neuroendocrine signaling. eLIFE. 4, e10110 (#co-corresponding).