Research (in English)
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. Choi W., Ryu SE., Cheon Y., Park YJ., Kim S., Kim E., Koo JH., Choi H., Moon C.#, Kim K.# (2021) A single chemosensory GPCR is required for a concentration-dependent behavioral switching in C. elegans. Current Biology. DOI : 10.1016/j.cub.2021.11.035 (#co-corresponding)
2. 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)
3. 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.
4. 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.
5. 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-¥â 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).