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Yimin Zou"Axon guidance and spinal cord injury"

Abstract :


Although many axon guidance molecules and their receptors have been identified, our understanding on signal transduction mechanisms leading to directional choice of axon turning is still very fragmented and rudimentary.
In the past few years, we began to gather evidence that the robust cell polarity signaling systems (apical-basal and planar polarity) mediate Wnt signaling in growth cone steering. We found that aPKC, a key component of apical-basal polarity signaling mediated Wnt attraction in anterior turning of commissural axons. We also found that Vangl2 and Disheveled1, members of the planar cell polarity (PCP) signaling pathway, antagonize each other in regulating Frizzled3 in planar polarity signaling. Vangl2 
promotes Frizzled3 internalization and reduces Frizzled3 phosphorylation while Disheveled1 promotes Frizzled3 cell surface membrane localization and hyperphosphorylation. Further more, Vangl2 is localized to the tips of extending growth cone filopodia, suggesting that the filopodia tips have the most active PCP signaling involving Frizzled3 endocytosis. I will report our new studies on how apical-basal and planar polarity signaling interact with each other 
in growth cones and how the interaction of these two cell polarity signaling pathways leads to signal amplification in the growth cone. These observations provide novel signaling and cell biological mechanisms in axon guidance. A few years ago, we found that the Wnt signaling system is reinduced after spinal cord injury in adulthood and cause corticospinal tract axon retraction and inhibits axon plasticity. I will also talk about our latest progress showing that 
the reinduced Wnt signaling system limits the regenerative potential in the conditioning lesion model of the sensory axons. We have also obtained evidence of improved functional recovery by blocking Wnt mediated inhibition.

Selected publications

1. Edmund Hollis II and Yimin Zou. Expression of the Wnt signaling system in central nervous system axon guidance and regeneration. Front Mol Neurosci. 2012;5:5. Epub 2012 Feb 2.

2. 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.

3. Beth Shafer, Charles Lo, Keisuke Onishi and Yimin Zou. Vangl2 Promotes Wnt/Planar Cell Polarity-like Signaling by Antagonizing Dvl1-Mediated Feedback Inhibition in Growth Cone Guidance. Developmental Cell. 2011 Feb 15;20(2):177-91.

4. Ali G. Fenstermaker, Asheeta Prasad, Ahmad Bechara, Youri Adolfs, Fadal Tissir, Andre Goffinet, Yimin Zou, Y*, 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.

5. Barry Dickson and Yimin Zou. Navigating intermediate targets: the nervous system midline. Chapter in Cold Spring Harbor Perspectives in Biology "Neuronal Guidance". 2010.

Anna I. Lyuksyutova, Chin-Chun Lu, Nancy Milanesio, Leslie A. King, Nini Guo, Yanshu Wang, Jeremy Nathans, Marc Tessier-Lavigne and Yimin Zou*. Anterior-posterior guidance of commissural axons by Wnt-Frizzled signaling. Science. 2003. 302, 1984-1988. (Evaluated by Faculty of 1000 Biology).

Scientific focus :

My lab is interested in molecular and cellular mechanisms of neural circuit development. We are studying how axons find their synaptic targets and how synapse formation is regulated. We are also studying how axons in the central nervous system cannot regenerate and how manipulating signaling pathways that control axon growth can allow us to promote repair and functional recovery.

Nathalie Sans