Yishi Jin
Professor
Section of Neurobiology
Department of Cellular and Molecular Medicine, SOM
Investigator, Howard Hughes Medical Institute, UCSD
e-mail: yijin@ucsd.edu
Lab Homepage: Jin Lab
How is a neuron guided to their partner? Neurons rely on specialized subcellular structures, called growth cones, to be guided to their targets. Through forward genetic screens, we have identified several max genes (for motor neuron axon guidance). One of the genes, max-1, defines a family of evolutionarily conserved proteins that function to modulate the netrin-signaling pathway. In our recent work, we have begun to investigate how axons are guided to their targets after injury.
How does a neuron form synapses with its partners? Synapses are the means that neurons use to communicate with others. At the presynaptic terminal, neurons develop elaborate subcellular structures to facilitate the accumulation and release of synaptic vesicles. Although much of the progress has been made in understanding neurotransmitter release, how the cytoarchitecture of a presynaptic terminal is built is nearly unknown. Using fluorescent markers that label different components of presynaptic terminals, we have isolated mutants that display abnormal synaptic morphology. Our analyses have identified new signaling molecules that function through GTPases and ubiquitin-mediated protein degration to specify distinct spatial domains at presynaptic terminals.
How does neuronal circuit control locomotion? A central feature of C. elegans locomotion is a balanced excitation and inhibition to the body muscles, as the result of coordinated action of cholinergic and GABAergic signaling through the motor neurons. We are examining the roles of a family of neuronal ACh receptors in modulating the excitation state of these two types of neurons using a combination of functional imaging and molecular genetic manipulations. Our analysis of a genetic mutation has also led us to establish a model for epilepsy.
How do nerves regenerate? Understanding how neural circuit forms during normal development has direct implications to the process of how injured neurons recover and regain function in mature animals. We have developed an ultrafast laser-based microsurgery procedure to perform axotomy in C. elegans neurons. The severed axons exhibit robust regrowth within 12-24 hours of surgery. We have identified numerous pathways regulating the rate and accuracy of adult axon regeneration.
Stawicki, T.M., Zhou, K., Yochem J., Chen, L., and Jin, Y. (2011). TRPM channels modulate epileptic-like convulsions via systemic ion homeostasis. Current Biology 21(10):883-888.
Van Epps, H., Dai, Y., Qi, Y. B., Goncharov, A., and Jin, Y. (2010). Nuclear pre-mRNA 3’ end cleavage and polyadenylation regulate synapse and axon development in C. elegans. Development, 137:2237-2250.
Yan, D., Wu, Z., Chisholm, A. D., and Jin, Y. (2009). The DLK-1 kinase promotes mRNA stability and local translation in synapses and axon regeneration. Cell 138:1005-1018.
Jospin, M., Stawicki, T., Qi, Y.B., Boulin, T., Horvitz, H. R., Bessereau, J. L., Jorgensen, E., and Jin, Y. (2009). An neuronal acetylcholine receptor regulates C. elegans locomotion. PLoS Biol. Dec;7(12):e1000265.
Nakata, K., Abrams, B., Grill, B., Goncharov, A., Huang, X., Chisholm, A. D., and Jin, Y. (2005). Regulation of a DLK-1 and p38 MAP kinase pathway by the ubiquitin ligase RPM-1 is required for presynaptic development. Cell 120:407-420.
Yanik, M. F., Cinar, H., Cinar, H. N., Chisholm, A. D., Jin, Y., and Ben-Yakar, A. (2004). Neurosurgery: functional regeneration after laser axotomy. Nature 432:822.
Hallam. S. J., Goncharov, A., McEwen, J., Baran, R., and Jin, Y. (2002). The C. elegans SYD-1, a presynaptic protein with PDZ, C2 and rhoGAP domains, specifies axon identity. Nature Neuroscience 5:1137-1146.
Huang, X., Cheng, H.-J., Tessier-Lavigne, M., and Jin, Y. (2002). MAX-1, a novel PH/Myth4/FERM domain cytoplasmic protein implicated in netrin-mediated axon repulsion. Neuron 34:563-576.
Zhen, M., Huang, X., Bamber, B., and Jin, Y. 2000. Regulation of presynaptic terminal organization by C. elegans RPM-1, a putative guanine nucleotide exchanger with a Ring-H2 finger domain. Neuron 26:331-343.
Zhen, M., and Jin, Y. 1999. The liprin protein SYD-2 regulates the differentiation of presynaptic termini in C. elegans. Nature 401:371-375.
Hallam, S.J., and Jin, Y. 1998 lin-14 regulates the timing of synaptic remodelling in Caenorhabditis elegans. Nature 395:78-82.
Relevant reviews
Wang, Z., and Jin, Y. (2010). Genetic analysis of axon regeneration. Curr. Opin. Neurobiol. 21:1-8.
Jin, Y. and Garner, C. C. (2008). Molecular mechanisms of presynaptic differentiation. Annual Review of Cell and Development 24:237-262.
Dr. Jin received her B.S. degree from Peking University, China, and her Ph.D. from the University of California, Berkeley. She completed her postdoctoral training at MIT.
