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Yimin Zou

Research

Axon Guidance

We are interested in the guidance cues that provide directional information for axon wiring and identified the Wnt family proteins as key guidance molecules along the major axes of the central nervous system for axon pathfinding and topographic mapping. We are currently studying how these guidance cues are laid out in concentration gradients and how axonal growth cones recognize and respond to these gradients. We found that the conserved apical-basal and planar cell polarity pathways mediate growth cone turning and an apical-basal polarity signaling component, aPKC, promotes the endocytosis of a Wnt/planar cell polarity component, Frizzled3. We are testing whether this is part of an amplification mechanism for asymmetric signaling to polarize growth cones.

Circuit repair after traumatic injury

Traumatic injuries of the adult 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. A 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.

Synapse formation and neurodevelopmental disorders

The signaling mechanisms that assemble neuronal synapses have been elusive. Our recent finding suggests that planar cell polarity signaling components 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.

Select Publications

  • Yue Ban, Ting Yu, Bo Feng, Charlotte Lorenz, Xiaojia Wang, Clayton Baker, Yimin Zou. Prickle promotes the formation and maintenance of glutamatergic synapses by stabilizing the intercellular planar cell polarity complex. Science Advances. 2021 Oct 8;7(41):eabh2974. doi: 10.1126/sciadv.abh2974. Epub 2021 Oct 6. PMID: 34613779
  • Yue Ban, Ting Yu, Jingyi Wang, Xiaojia Wang, Can Liu, Clayton Baker and Yimin Zou. Mutation of the murine Prickle1 (R104Q) causes phenotypes analogous to human symptoms of epilepsy and autism. Experimental Neurology. 2021 Sep 28:113880. doi: 10.1016/j.expneurol.2021.113880. Online ahead of print. PMID: 34597683
  • Bo Feng, Andiara E. Freitas, Lilach Gorodetski, Jingyi Wang, Runyi Tian, Yeo Rang Lee, Akumbir S. Grewal and Yimin Zou. Planar cell polarity signaling components are a direct target of β-amyloid–associated degeneration of glutamatergic synapses. Sci Adv. 2021 Aug 18;7(34):eabh2307. doi: 10.1126/sciadv.abh2307. Print 2021 Aug. PMID: 34407949.
  • Yimin Zou. Targeting axon guidance cues for neural circuit repair after spinal cord injury. J Cereb Blood Flow Metab. 2021 Feb;41(2):197-205. doi: 10.1177/0271678X20961852. Epub 2020 Nov 9. PMID: 33167744.
  • Keisuke Onishi, Runyi Tian, Bo Feng, Yiqiong Liu, Junkai Wang, Yinan Li, and Yimin Zou. LRRK2 mediates axon development by regulating Frizzled3 phosphorylation and growth cone–growth cone communication. Proc Natl Acad Sci U S A. first published July 8, 2020 https://doi.org/10.1073/pnas.1921878117.
  • Yimin Zou. Breaking symmetry - cell polarity signaling pathways in growth cone guidance and synapse formation. Curr Opin Neurobiol. 2020 Apr 29;63:77-86. doi: 10.1016/j.conb.2020.03.010. Online ahead of print. PMID: 32361599
  • John Scott, Sonal Thakar, Ye Mao, Huaping Qin, Helen Hejran, Su-Yee Lee, Ting Yu, Olga Klezovitch, Hongqiang Cheng, Yongxin Mu, Sourav Ghosh, Valeri Vasioukhin, and Yimin Zou.Apical-basal polarity signaling components, Lgl1 and aPKCs, control glutamatergic synapse number and function. iScience. 2019 Sep 9;20:25-41. doi: 10.1016/j.isci.2019.09.005. [Epub ahead of print] (PMID:31546104)
  • Keisuke Onishi and Yimin Zou. Sonic Hedgehog switches on Wnt/planar cell polarity signaling in commissural axon growth cones by reducing levels of Shisa2. Elife. 2017 Sep 8;6. pii: e25269. doi: 10.7554/eLife.25269.
  • 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. 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 (2012). Does planar cell polarity signaling steer growth cones? Curr. Top. Dev. Biol. 101:141-160.
  • Edmund Hollis II and Yimin Zou (2012). Reinduced Wnt signaling limits regenerative potential of sensory axons in the spinal cord following conditioning lesion. Proc. Natl. Acad. Sci. USA 109(36):14663-14668.
  • Edmund Hollis II and Yimin Zou (2012). Expression of the Wnt signaling system in central nervous system axon guidance and regeneration. Front. Mol. Neurosci. 5:5.
  • Yimin Zou (2011). When it is hard to get to with genetics--planar cell polarity under a chemical scalpel. Chem. Biol. 18(11):1350-1351.
  • Beth Shafer, Keisuki Onishi, Charles Lo, Gulsen Colakoglu, Zou Y. (2011). Vangl2 promotes Wnt/planar cell polarity-like signaling by antagonizing Dvl1-mediated feedback inhibition in growth cone guidance. Devel. Cell 20(2):177-191.
  • Ali G. Fenstermaker, Asheeta A. Prasad, Ahmad Bechara, Youri Adolfs, Fadel Tissir, Andre Goffinet, Yimin Zou, and R. Jeroen Pasterkamp (2010). Wnt/Planar cell polarity signaling controls the anterior-posterior organization of monoaminergic axons in the brainstem. J. Neurosci. 30(47):16053-16064.
  • Barry J. Dickson and Yimin Zou (2010). 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 and Yimin Zou (2010). Sonic hedgehog induces response of commissural axons to Semaphorin repulsion during midline crossing. Nature Neurosci. 13:29-35 (doi:10.1038/nn.2457).
  • Esther Stoeckli and Yimin Zou (2009). How are neurons wired to form functional and plastic circuits? Meeting on Axon Guidance, Synaptogenesis and Neural Plasticity (Cold Spring Harbor Laboratories). EMBO J. 10(4):326-330.
  • Yimin Zou (2009). Axons find their way in the snow. Development 136:2135-2139.
  • Elizabeth K. Davis, Yimin Zou, and Anirvan Ghosh (2008). Wnts acting through canonical and noncanonical signaling pathways exert opposite effects on hippocampal synapse formation. Neural Development 3:32.
  • Yaobo Liu, Xiaofei Wang X, Chin-Chun Lu, Rachel Kerman, Oswald Steward, Xiao-Ming Xu, and Yimin Zou. (2008). Repulsive Wnt signaling inhibits axon regeneration after CNS injury. J. Neurosci. 28:8376-8382.
  • Patricia C. Salinas and Yimin Zou (2008). Wnt Signaling in neural circuit assembly. Annu. Rev. Neurosci. 31:339-358.
  • 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. J. Neurosci. 28:3456-3467.
  • Yimin Zou and Anya I. Lyuksyutova (2007). Morphogens as conserved axon guidance cues. Curr. Opin. Neurobiol. 17:22-28.
  • Yimin Zou. (2006). Navigating the anterior-posterior axis with Wnts. Neuron. 49(6):787-789.
  • 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):31-37.
  • Lee Fradkin, Gian Garriga , Patricia C. Salinas, John Thomas, Xiang Yu and Yimin Zou (2005). Wnt signaling in neural circuit development (minireview). J. Neurosci. 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 Neurosci. 8(9):1151-1159.
  • Yimin Zou (2004). Wnt signaling in axon guidance (review). Trends Neurosci. 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):1976-1982.
  • 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.

Biography

Yimin Zou graduated from Shanghai Fudan University and was a CUSBEA (China and United States Biochemistry Examination and Application Program) student and received his Ph. D. from University of California, Davis and San Diego, in 1995. He did his postdoctoral fellowship at University of California, San Francisco from 1996 to 2000 and was an Assistant and Associate Professor at the University of Chicago from 2000 to 2006. He joined the faculty in July, 2006.

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