Yishi Jin
Professor
Section of Neurobiology
Department of Neurosciences
Investigator, Howard Hughes Medical Institute, UCSD
e-mail: yijin@ucsd.edu
Lab Homepage: Jin Lab
How are specific types of GABAergic neurons generated? We are interested in the molecular program controlling the generation of GABAergic motor neurons. These neurons modulate the locomotion of the worm. We have identified several transcription factors, including the UNC-30 homeodomain protein, the CND-1 HLH protein and the AHR-1 aryl hydrocarbon receptor that control specific aspects of the GABAergic property of these neurons. We are combining genomic and computational approaches to define the expression profile for these neurons and to establish the transcriptional network.
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. Our recent work has begun to elucidate the cellular trafficking mechanisms underlying the growth cone guidance.
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 XFP 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 do synaptic connections remodel? An intriguing feature of several GABA neurons is that they remodel their synaptic connections during development. This remodeling is unusual because it involves a complete reversal of information flow without dramatic changes in neuronal morphology. We are particularly interested in exploring this phenomena in the hope that our analysis will shed light on other types of synaptic plasticity that are related to growth, aging, learning and memory. We have found that a nuclear protein LIN-14 controls the timing of the remodeling cell autonomously. Low levels of LIN-14 cause these neurons to remodel early; high levels of LIN-14 delay and prevent remodeling. We are addressing how the regulation of LIN-14 is controlled.
How does motor circuit control locomotion? A central feature of C. elegans locomotion is 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.
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 are characterizing the factors regulating the rate and accuracy of adult axon regeneration.
Brown, H. M., Van Epps, H., Goncharov, A., Grant, B., and Jin, Y. (2008). The JIP3 scaffold proien UNC-16 regulates RAB-5 dependent membrane trafficking at C. elegans synapses. Dev. Neurobiol., in press.
Jin, Y. and Garner, C. C. (2008). Molecular mechanisms of presynaptic differentiation. Annual Review of Cell and Development 24:237-262.
Grill, B., Bienvenut W. V., Brown, H. M., Ackley, B. D., Quadroni, M., and Jin, Y. (2007). C. elegans RPM-1 Regulates Axon Termination and Synaptogenesis through the Rab GEF, GLO-4, and the Rab GTPase, GLO-1. Neuron 55:587-601.
Wu, Z., Ghosh Roy, A., Yanik, M. F., Zhang, J. Z., Jin, Y., and Chisholm, A. D. (2007). C. elegans neuronal regeneration is influenced by life stage, ephrin signaling and synaptic branching. PNAS 104:15132-15137.
Dai, Y., Taru, H., Deken, S. L., Grill, B., Ackley. B, Nonet, M. L., and Jin, Y. (2006). SYD-2 Liprin protein organizes presynaptic active zone formation through ELKS. Nature Neuroscience 9:1479-1487.
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.
Cinar, H., Keles, S., and Jin, Y. (2005). Cellular identity of GABAergic neurons in Caenorhabditis elegans. Current Biology 15:340-346.
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.
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.
Dr. Jin received the B.S. degree from Peking University, China, and the Ph.D. from the University of California, Berkeley. She completed her postdoctoral training at MIT.