Yimin Zou, PhD

Yimin Zou, PhD

Professor and Chair
Section of Neurobiology
Division of Biological Sciences

Contact Information

9500 Gilman Drive
Pacific Hall - Room 1224A
Office tel: 858-534-7212
Lab tel: 858-534-7213
Fax: 858-534-6512
Email: yzou@ucsd.edu
Lab Website: http://www.biology.ucsd.edu/labs/zou

Wiring and repair of neural circuits

We study how neurons form precise functional connections and the strategies to restore function following traumatic injury and correct abnormal behaviors in neurodevelopmental disorders.

1. Axon Guidance
We pioneered the finding that Wnt family proteins provide key directional information along the major axes of the nervous system for axon pathfinding and topographic projections. We are currently studying how these guidance cues are laid out in concentration gradients and how growth cones recognize and respond to these gradients. We were the first to show that the conserved apical-basal and planar cell polarity pathways mediate Wnt signaling in growth cone turning. We found that apical-basal polarity signaling component, aPKC, promotes the endocytosis of a planar cell polarity component, Frizzled3, and are testing whether it is part of an amplification mechanism for asymmetric signaling to polarize growth cones.

2. Circuit repair after traumatic injury
Traumatic injuries of the brain and the spinal cord lead to loss of many important functions. We found that the Wnt signaling pathways are reactivated after spinal cord injury. The reinduced Wnt inhibitory system limits motor and sensory axon growth and functional recovery. Our recent studies showed that combining molecular manipulation to enhance axon plasticity with behaviorally-guided training offers the maximal functional recovery. We are currently studying the network basis of neural circuit remodeling after spinal cord injury and traumatic brain injury.

3. Synapse formation and neurodevelopmental disorders
Our recent finding suggests that planar cell polarity signaling components are present in developing glutamatergic synapses and play essential roles in glutamatergic synapse formation. This opens up new opportunities to study synaptogenesis and plasticity, fundamental to understanding neural circuit function. Mutations in planar cell polarity genes, such as the Prickles, are associated with neurodevelopmental disorders, such as autism and epilepsy. We are studying the molecular and circuit mechanisms of these diseases and exploring strategies for therapeutic interventions.

Sonal Thakar, Liqing Wang, Ting Yu, Mao Ye, Keisuke Onishi, John Scott, Jiaxuan Qi, Catarina Fernandes, Darwin Berg and Yimin Zou*. Evidence for opposing roles of Celsr3 and Vangl2 in glutamatergic synapse formation. Proc Natl Acad Sci U S A. 2017 Jan 5. pii: 201612062. doi: 10.1073/pnas.1612062114. [Epub ahead of print] PMID: 28057866

Edmund Hollis 2nd, Nao Ishiko, Ting Yu , Chin-Chun Lu, Ariela Haimovich, Kristine Tolentino, Alisha Richman, Anna Tury, Shih-Hsiu Wang, Maysam Pessian, Euna Jo, Alex Kolodkin and Yimin Zou. Ryk controls remapping of motor cortex during functional recovery after spinal cord injury. Nature Neurosci. 2016 May;19(5):697-705

Edmund R Hollis II, Nao Ishiko, Maysam Pessian, Kristine Tolentino, Corinne A. Lee-Kubli, Nigel A. Calcutt and Yimin Zou. Remodeling of spared proprioceptive circuit of a small number of neurons supports major functional recovery. Nature Communications. 2015 Jan 19;6:6079. doi: 10.1038/ncomms7079.

Edmund R Hollis II, Nao Ishiko, Kristine Tolentino, Ernest Doherty, Maria J. Rodriguez, Nigel Calcutt and Yimin Zou. A novel and robust pre-conditioning lesion induced by ethidium bromide. Experimental Neurology. Exp Neurol. 2014 Dec 23. pii: S0014-4886(14)00389-6.

Keisuke Onishi, Edmund Hollis and Yimin Zou. Axon guidance and injury-lessons from Wnts and Wnt signaling. Curr Opin Neurobiol. 2014 Aug;27C:232-240.

Keisuke Onishi, Beth Shafer, Charles Lo, Fadel Tissir, Andre M. Goffinet, and Yimin Zou. Antagonistic Functions of Dishevelleds Regulate Frizzled3 Endocytosis via Filopodia Tips in Wnt-Mediated Growth Cone Guidance. The Journal of Neuroscience, December 4, 2013 * 33(49):19071-1908.

Anna Tury, Kristine Tolentino and Yimin Zou. Altered expression of atypical PKC and Ryk in the spinal cord of a mouse model of amyotrophic lateral sclerosis. Dev Neurobiology 2013 Oct 7. doi: 10.1002/dneu.22137

Yimin Zou. Does planar cell polarity signaling steer growth cones Current Topics in Developmental Biology. 2012;101:141-60.

Edmund Hollis II and Yimin Zou. Reinduced Wnt signaling limits regenerative potential of sensory axons in the spinal cord following conditioning lesion.Proc Natl Acad Sci U S A. 2012 Sep 4;109(36):14663-8

Edmund Hollis II and Yimin Zou. Expression of the Wnt signaling system in central nervous system axon guidance and regenerationFront Mol Neurosci. 2012;5:5

Yimin Zou. When it is hard to get to with genetics--planar cell polarity under a chemical scalpel.Chem Biol. 2011 Nov 23;18(11):1350-1.

Beth Shafer, Keisuke Onishi, Charles Lo, Gulsen Colakoglu, and Yimin Zou. Vangl2 Promotes Wnt/Planar Cell Polarity-like Signaling by Antagonizing Dvl1-Mediated Feedback Inhibition in Growth Cone Guidance. Developmental Cell. 15 February 2011 20(2): 177-191.

Ali G. Fenstermaker, Asheeta A. Prasad, Ahmad Bechara, Youri Adolfs, Fadel Tissir, Andre Goffinet, Yimin Zou, and R. Jeroen Pasterkamp. Wnt/Planar Cell Polarity Signaling Controls the Anterior-Posterior Organization of Monoaminergic Axons in the Brainstem. Journal of Neuroscience. 2010 30(47):16053-16064

Barry J. Dickson and Yimin Zou. Navigating Intermediate Targets: The Nervous System Midline. Cold Spring Harbor Perspectives in Biology. Published in Advance June 9, 2010 (doi: 10.1101/cshperspect.a002055)

Liseth M Parra & Yimin Zou (2009). Sonic hedgehog induces response of commissural axons to Semaphorin repulsion during midline crossing. Published online: 29 November 2009 | doi:10.1038/nn.2457.

Zou Y. (2009). Axons find their way in the snow. Development 2009 136:2135-2139.

Stoeckli E, Zou Y. (2009). How are neurons wired to form functional and plastic circuits? Meeting on Axon Guidance, Synaptogenesis & Neural Plasticity. EMBO Rep. 2009 Apr;10(4):326-30. Epub 2009 Mar 20.

Salinas PC, Zou Y. (2008). Wnt signaling in neural circuit assembly. Annual Review of Neuroscience. 31:339-58.

Yaobo Liu, Xiaofei Wang, Chin-Chun Lu, Rachel Kerman, Oswald Steward, Xiao-Ming Xu, and Yimin Zou. (2008). Repulsive Wnt Signaling Inhibits Axon Regeneration after CNS Injury. Journal of Neuroscience. 28: 8376-8382.

Alex M. Wolf, Anna I. Lyuksyutova, Ali G. Fenstermaker, Beth Shafer, Charles G. Lo, and Yimin Zou. (2008). Phosphatidylinositol-3-Kinase-Atypical Protein Kinase C Signaling Is Required for Wnt Attraction and Anterior-Posterior Axon Guidance. Journal of Neuroscience. 28: 3456-3467.

Zou Y., Lyuksyutova AI. (2007) Morphogens as conserved axon guidance cues. Curr Opin Neurobiol. Feb;17(1):22-8.

Yimin Zou. (2006). Navigating the anterior-posterior axis with Wnts. Neuron. 49(6):787-9.

Adam Schmitt, Jun Shi, Alex Wolf, Chin-Chun Lu, Leslie A. King and Yimin Zou. (2006). Wnt-Ryk signaling mediates medial-lateral retinotectal topographic mapping. Nature 439(7072);31-7.

Lee Fradkin, Gian Garriga , Patricia C. Salinas, John Thomas, Xiang Yu and Yimin Zou. (2005) Wnt signaling in neural circuit development (minireview). Journal of Neuroscience. 25(45):10376-10378.

Yaobo Liu, Jun Shi, Chin-Chun Lu, Zheng Bei Wang, Anna I. Lyuksyutova, Xuejun Song and Yimin Zou. (2005) Ryk-mediated Wnt repulsion regulates posterior-directed growth of corticospinal tract. Nature Neuroscience. 8(9):1151-9.

Yimin Zou (2004). Wnt signaling in axon guidance (review). Trends in Neuroscience; 27(9): 528-532.

Yimin Zou, Florian Engert and Huizhong W. Tao. (2004). The Assembly of Neural Circuits (Meeting Report). Neuron, 43(2):159-163.

Anna I. Lyuksyutova, Chin-Chun Lu, Nancy Milanesio, Leslie A. King, Nini Guo, Yanshu Wang, Jeremy Nathans, Marc Tessier-Lavigne and Yimin Zou. (2003) Anterior-posterior guidance of commissural axons by Wnt-frizzled signaling. Science, 302:1984-1988.

Elke Stein, Yimin Zou, Mu-ming Poo, and Marc Tessier-Lavigne. (2001). Netrin-1 binds DCC to stimulate axon outgrowth and turning independent of adenosine A2B receptor activation. Science, 291 (5510):1976-82.

Yimin Zou, Esther Stoeckli, Hang Chen, and Marc Tessier-Lavigne. (2000). Squeezing axons out of the gray matter: A role for slit and semaphorin proteins from midline and ventral spinal cord Cell, 102:363-375.

Hang Chen, Anil Bagri, Joel A. Zupicich, Yimin Zou, Esther Stoeckli, Samuel J. Pleasure, Daniel H. Lowenstein, William C. Skarnes, Alain Chedotal, and Marc Tessier-Lavigne. (2000). Neuropilin-2 regulates the development of select cranial and sensory nerves and hippocampal mossy fiber projections. Neuron, 25(1): 43-56.

Yimin Zou. Does planar cell polarity signaling steer growth cones? Curr Top Dev Biol. 2012;101:141-60.