Symposium at the Institute of Neuroscience in Shanghai on Frontiers in axon guidance and regeneration Abstracts
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| Symposium at the Institute of Neuroscience in Shanghai
on Frontiers in axon guidance and regeneration Abstracts 1. Alex Kolodkin HHMI Department of Neuroscience Johns Hopkins University USA
Kolodkin, AL HHMI and The Solomon H. Snyder Department of Neuroscience, The Johns Hopkins School of Medicine, 725 N. Wolfe St./1001 PCTB, Baltimore, MD 21205, USA Neurons are guided to their targets through the action of guidance cues. The response to these cues is dependent on both cell surface and cytosolic components that participate in signaling events critical for altering cytoskeletal dynamics and establishing appropriate neuronal trajectories. We have investigated how motor neurons in both vertebrates and invertebrates are guided to their targets through the action of semaphorin guidance cues. In the mouse, these studies establish the importance of semaphorin holoreceptor composition in regulating the timing of motor axon outgrowth, motor axon fasciculation at key choice points, and peripheral pathfinding events essential for the generation of neuromuscular connectivity. In Drosophila, we have investigated signaling events that follow transmembrane semaphorin activation of neuronal plexin semaphorin receptors. We have shown that semaphorin-plexin signaling is crucial for motor axon guidance in Drosophila, and this has allowed us to investigate the roles played by novel cytosolic signaling components in axon guidance. Our recent analysis of the MICAL (molecule that interacts with CasL) protein has allowed us to investigate how integrin and semaphorin signaling are integrated following plexin receptor activation. Cas (Crk-associated substrate) proteins play important roles downstream of integrin receptor activation. We have taken advantage of Drosophila genetics to disrupt Cas signaling and also interactions between the Cas and MICAL proteins. These studies establish a crucial role for plexin activation and Cas function in repulsive motor axon guidance, and they provide a framework for understanding the role played by integrin signaling in these guidance events. Together, these studies on semaphorin-mediated motor axon guidance show how cell-surface and cytosolic guidance cue signaling components collaborate to establish motor neuron circuitry during development. 2. Alain Chedotal Professor Université Paris 6 France
Role of slits and semaphorins in the development of the cerebellar system Progenitors in the neuroepithelium lining the roof of the fourth ventricle, the so-called rhombic lip, generates all hindbrain precerebellar neurons (pons, lateral reticular nucleus, external cuneatus nucleus and inferior olive) and cerebellar granule cells. We have studied the function of slits and semaphorins in the development of rhombic lip derivatives. We found that the migration of all precerebellar neurons is controlled by slits and their receptor roundbout (robo). In particular the choice of these inferior olivary neurons or not to cross the midline is regulated by interactions between Rig1/robo3 and Robo1/Robo2. Likewise, slit1/slit2 and robo1/Robo2 orient the migration pathway of pontine neurons from the rhombic lip to the floor plate. We next studied the development of cerebellar granule cells. The molecular control of the transition between proliferation and differentiation in cerebellar granule cells is largely unknown. We showed that the transmembrane receptor Plexin-B2 is expressed by proliferating granule cell progenitors. Using Plexin-B2 knockout mice, we found that Plexin-B2 controls the balance between proliferation and differentiation in granule cells. last, we showed that the transmembrane semaphorin Sema6A and its receptor plexin-A2 control the initiation of granule cell radial migration probably through a modulation of nuclear/soma translocation. 3. Marie Filbin Distinguished Professor Hunter College USA
One of the major impediments to axonal regeneration after injury is inhibitors in myelin. Three myelin inhibitors have been identified in, NogoA, MAG and OMgp. One approach to overcome these inhibitors to encourage regeneration is to change the intrinsic state of the axon such that it no longer recognizes these molecules as inhibitory. We have shown that if the neuronal cAMP levels are elevated either artificially with an analogue such as db cAMP or by priming neurons with a variety of neurotrophins (NGF, BDNF) before exposure to the inhibitor, MAG and myelin in general no longer inhibit axonal growth. Furthermore, we have also shown that the long-recognized ability of spinal dorsal column axons to regenerate if the peripheral branch of the same neuron is lesioned beforehand is a consequence of a transient increase in endogenous cAMP levels in the DRG cell bodies. Importantly, injection of db cAMP directly into the DRG in the absence of a conditioning lesion, is sufficient to induce regeneration of subsequently lesioned dorsal column axons. This cAMP effect is transcription dependent and we have identified 4 very different genes that are up-regulated in response to either elevation of cAMP or a conditioning lesion. All 4 of these proteins block inhibition by myelin and they are currently being tested for their ability to promote regeneration in vivo. 4. Yimin Zou Associate Professor Department of Neuroscience University of Chicago USA
Nervous system functions rely on precisely patterned network of connections. During development axons undergo remarkable pathfinding and target selection to allow the formation of specific synaptic connections. We found that Wnt family proteins provide directional information of pathfinding of ascending sensory axons and descending motor axons along the anterior-posterior axis in the spinal cord. We also found that Wnt3 plays important roles in topographic mapping as a counterbalancing force againt ephrinB1 in medial-lateral retinotectal mapping. Therefore, Wnts may contribute significantly to nervous system wiring. Appendix: short CVs of the four speakers with a selection of 5 publications from each speaker see next pages. CURRICULUM VITAE ALEX LEO KOLODKIN Department of Neuroscience Johns Hopkins University School of Medicine 725 N. Wolfe Street/813 WBSB Baltimore, MD 21205 Phone (410) 614-9499 FAX (410) 614-8423 e-mail: kolodkin@jhmi.edu
DEGREES AWARDEDPh.D. 1987, Institute of Molecular Biology, University of Oregon, Eugene, Oregon Thesis Title: Double Strand Breaks Can Initiate Meiotic Recombination in S. cerevisiae (Franklin W. Stahl, advisor) B.A. 1980, Wesleyan University, Middletown, Connecticut PROFESSIONAL EXPERIENCE Investigator, Howard Hughes Medical Institute, 7/2005–present Professor, Department of Neuroscience (secondary appointment in Department of Molecular Biology), The Johns Hopkins School of Medicine, Baltimore Maryland, 6/04-present Associate Professor, Department of Neuroscience (secondary appointment in Department of Molecular Biology), The Johns Hopkins School of Medicine, Baltimore Maryland, 1/00-6/04 Assistant Professor, Department of Neuroscience (secondary appointment in Department of Molecular Biology), The Johns Hopkins School of Medicine, Baltimore, Maryland, 1/95-12/99 Postdoctoral Research Fellow, Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley, California (Corey S. Goodman, advisor),1987-1994 Graduate Trainee, Institute of Molecular Biology, University of Oregon, Eugene, Oregon (Franklin W. Stahl, advisor), 1983-1987 Graduate Teaching Fellow, Department of Biology, University of Oregon, 1982-1983 Research Associate, Department of Radiobiology (K. Brooks Low, advisor), Yale University, New Haven, Connecticut 1980-1982 Undergraduate Research Assistant, Department of Biology, Wesleyan University, Middletown. Connecticut (Robert S. Turner, advisor) 1978-1980 ACADEMIC HONORS AND RESEARCH AWARDS HHMI Investigator, 2005–present The Streisinger Lecturer, U. of Oregon, Eugene, Invited speaker for annual lectureship, 2005 NIH (NINDS) P30 Award: JHMI Center for Neuroscience Research, 2005-2010 Javits Investigator Award, NINDS, 2004 National Alliance for Autism Research Award, 2004-2006 NIH (NINDS) R01: Semaphorin-mediated Growth Cone Guidance, 1996-2011 NIH (NIMH) R01: Neuropilins and the Molecular Basis of Repulsive Guidance, 1998-2009 Christopher Reeve Paralysis Foundation Award, 2003-2005 Johns Hopkins Center for ALS Research Investigator Award, 2000–2004 Kirsch Investigator Award, 2002-2004 McKnight Neuroscience Investigator Award, 2000-03 Whitehall Foundation Research Award, 1995-2000 Searle Scholars Award, 1996-1999 Fund for Medical Discovery, Johns Hopkins University Medical School, 1998 McKnight Neuroscience Scholar Award, 1995-1998 Klingenstein Fellowship Award in the Neurosciences, 1995-1998 Alfred P. Sloan Research Fellow, 1995-1997 Damon Runyon-Walter Winchell postdoctoral fellowship, 1987-1990 Jane Coffin Childs, NIH, and American Cancer Society postdoctoral fellowships; 1987 (declined) Undergraduate Research Award, Department of Biology, Wesleyan University, 1980 Giffon Prize, Department of Religious Studies, Wesleyan University, 1980
Kantor, D.B., Chivatakarn, O., Peer, K.L., Oster, S.F., Inatani, M., Hansen, M.J., Flanagan, J.G., Yamaguchi, Y., Sretavan, D.W., Giger, R.J., and Kolodkin, A.L. (2004). Semaphorin 5A is a Bifunctional Axon Guidance Cue Regulated by Heparan and Chondroitin Sulfate Proteoglycans. Neuron, 44, 961-975. Terman, J.R., and Kolodkin, A.L. (2004). The AKAP Nervy directly couples Protein Kinase A to Plexin mediated semaphorin repulsion. Science, 303, 1204-1207.
Terman, J.R., Mao, T., Pasterkamp, R.J., Yu, H.-H., and Kolodkin, A.L. (2002). MICALs, a Family of Conserved Flavoprotein Oxidoreductases, Function in Plexin-Mediated Axonal Repulsion. Cell 109, 887-900 (cover article).
tel: +33-144273447/144272130, fax: +33-144272669; e-mail: chedotal@infobiogen.fr born: September 18, 1967 Education and University Titles 1988-1993 Student Ecole Normale Supérieure de Lyon 1988-1989 Licence in Animal Biology, Lyon 1 University 1989-1990 Master in Physiology-Neuroscience, Lyon 1 University 1990-1991 DEA in Neuroscience, University Paris VI (adv. Constantino Sotelo) Expression of CGRP during the development of the olivocerebellar projection 1992-1995 Ph.D. in Neuroscience, University Paris VI (adv.Constantino Sotelo) Development of the rat olivocerebellar projection Other Research experience 1991-1992 Research fellow in the laboratory of Cerebrovascular Research, Montreal Neurological Institute (adv. Edith Hamel) Cholinergic and VIPergic Innervation of cortical blood vessels 1995-1997 Postdoctoral, Department of Molecular and Cellular Biology, UC Berkeley (adv. Corey S. Goodman) Semaphorins and neuropilins in vertebrate brain development Honors and Awards 1995-1997 EMBO Long Term Fellowship 2000 ACI " jeune Chercheur " of the French Ministery of Research 2001 Young Investigator Award, European Society for Neurochemistry Professional Activities 1997-2001 Chargé de Recherche 2ème classe (CR2), INSERM U106, Paris, France 09/2001 12/2002 Directeur de Recherche 2ème classe (DR2) and Group Leader, INSERM U106, Paris, France 01/2003- Directeur de Recherche 2ème classe (DR2) and Group Leader, CNRS UMR7102, Paris, France 5 Publications Nguyen Ba-Charvet K.T., K. Brose, V. Marillat, T. Kidd, C.S. Goodman, M. Tessier-Lavigne, M., C. Sotelo and A. Chédotal (1999) Slit-2 mediated repulsion and collapse of developing forebrain axons. Neuron 22, 463-473. Soussi-Yanicostas N., F. De Castro, K. Julliard, I. Perfettini, A. Chédotal and C. Petit. (2002) Anosmin-1, defective in the X-linked form of Kallmann syndrome, promotes axonal branch formation of the olfactory bulb output neurons, Cell 109: 217-228. 18. Marillat V., Sabatier C., Failli V., Matsunaga E., Sotelo C., Tessier-Lavigne M. and Chédotal A (2004) The Slit receptor Rig-1/Robo3 controls the development of precerebellar neurons. Neuron, 43: 69-79. Matsunaga E., Tauszig-Delamasure S., Monnier P.P., Müeller B.K., Strittmatter S.M., Mehlen P. and Chédotal A. (2004) RGM and its receptor neogenin regulate neuronal survival. Nature Cell Biol. 6, 749-755. Kerjan G, Dolan J, Haumâitre C, Schneider-Maunoury S, Fujisawa H, Mitchell K, Chedotal A (2005) The transmembrane semaphorin Sema6A controls cerebellar granule cell migration Nat Neurosci. 8:1516-1524.
EXPERIENCE 1986-1990 - Research Associate, Department of Neurology, The Johns Hopkins University School of Medicine. 1990-1995 - Associate Professor, Department of Biological Sciences, Hunter College CUNY 1995-1997 - Professor, Department of Biological Sciences, Hunter College, CUNY 1997- - Marie L. Hesselbach Chair in Biology, Hunter College 1998- - Distinguished Professor of CUNY 2000- - Director, Specialized Neuroscience Research Program
1990- present: President New York Friends of Myelin 1995-2000: Established Investigator of the American Heart Association (NY) 1994-1996: Elected secretary to NYSEM (New York Soc. Experimental Microscopy) 1996-1999: Elected board member of NYSEM 1998: Norman Cohn award, MS Society (Highest scoring grant) 1999: President NYSEM 1999-2002: Elected council member for the American Society for Neurochemistry 2000: Grass Foundation Lecture, Univ. Minnesota 2001: Ameritec Prize for Research to Cure Paralysis 2002: Javits Investigator Awards (R37) 2002: Elected Chair of Gordon Conference on Myelin 2003 – 2007 Research Programs Advisory Council Member of National Multiple Sclerosis Society 2004 Presidential Lecture, American Neurological Association 2004 Society for Neuroscience Special lecture
1. Reviewing Editor: J. Neuroscience 2003 - 2. Associate Editor: Molecular and Cellular Neuroscience 1996- present • J. Neuroscience Research 1995- • Journal of Neuroscience 2003- • Experimental Neurology 2003 – 3. Reviewer: Nature, Cell, Science, Neuron, J. Cell Biol., J. Neurochem, Trends in Neurosci. J. Biol. Chem., Mol. and Cell Neurosci, J. Neurosci, J. Neurosci. Res., and Development Eur. J. Neurosci.
• Packard Center for ALS Research at Johns Hopkins, 2000- • Center for MS Research at Harvard, 2001- •The Burke Research Institute 2003- • Reeve-Irvine Research Center, UCI 2003- • Scientific Council of Ireland SELECT PUBLICATIONS 1. Mukhopadhyay, G., Doherty, P., Crocker, P., Walsh, F.S. and Filbin, M.T. (1994). A novel role for myelin associated glycoprotein as an inhibitor of axonal regeneration. Neuron 13:757-767. 2. Cai, D., Shen, Y., DeBellard, M., Tang, S. and Filbin,M.T. (1999) Prior exposure to neurotrophins blocks inhibition of axonal regeneration by MAG and myelin via a cAMP-dependent mechanism. Neuron 22:89-101. 3. Pearse, D.D., Pereira, F.C., Marcillo, A.E., Bates, M.L., Berrocal, Y.A., Filbin, M.T., and Bunge, M.B. (2004). cAMP and Schwann cells promote axonal growth and functional recovery after spinal cord injury. Nature Medicine 10:610-616 4. Gao, Y., Deng. , K, Nikulina, E., Hou, J., Bryson, J.B., Spencer, T., Mellado, W., Barco, A., Kandel, E.R., and Filbin, M.T., Activated CREB is sufficient to overcome inhibitors in myelin and promote spinal axon regeneration in vivo. Neuron 44:609-619. 5. Domeniconi, M., Zampieri, N., Spencer, T., Hilaire, M., Mellado, W., Chao, M.V., and Filbin, M.T. (2005). MAG Induces Regulated Intramembrane Proteolysis of the p75 Neurotrophin Receptor to Inhibit Neurite Outgrowth. Neuron 46:1-7. Yimin Zou, Ph. D. Associate Professor Department of Neurobiology, Pharmacology and Physiology The University of Chicago Phone: (773) 834-9087 Fax: (773) 834-3808 Email: yzou@bsd.uchicago.edu
Education
Research Experience05/06-present Associate Professor (with tenure), University of Chicago, Department of Neurobiology, Pharmacology and Physiology. Molecular and cellular mechanisms of axon pathfinding, branching and target selection in nervous system development. Control of cell polarity and motility in neuronal migration.
Neurobiology, Pharmacology and Physiology. Molecular and cellular mechanisms of axon pathfinding, branching and target selection in nervous system development. Control of cell polarity and motility in neuronal migration. 12/96-10/00: Postdoctoral Fellow, University of California, San Francisco. Molecular mechanisms of axon guidance. Midline pathfinding of commissural axons. Signaling mechanisms of chemorepulsive guidance. Advisor: Dr. Marc Tessier- Lavigne.
09/92-12/95: Doctoral Dissertation at the University of California, San Diego.
Title: “Transcriptional regulation of cardiac muscle-specific genes”. Advisor: Dr. Kenneth R. Chien. 09/89-08/92: Graduate Study and Laboratory rotations, Graduate Group in Biochemistry and Molecular Biology, University of California, Davis.
Fudan University, Shanghai, China. Eucaryotic gene expression. Advisor: Professor Shou-Yuan Zhao. Honors and Awards2003 Alfred P. Sloan Fellow 2003 W. M. Keck Foundation Research Achievement Award (Semi-finalist in Keck Young Scholar Competition) 2001 Schweppe Foundation Career Development Award 2001 March of Dimes Basil O’Connor Starting Scholar Research Award BibliographyYimin Zou, Esther Stoeckli, Hang Chen, and Marc Tessier-Lavigne*. Squeezing axons out of the gray matter: A role for slit and semaphorin proteins from midline and ventral spinal cord. Cell. 2000. 102, 363-375. Anna I. Lyuksyutova, Chin-Chun Lu, Nancy Milanesio, Leslie A. King, Nini Guo, Yanshu Wang, Jeremy Nathans, Marc Tessier-Lavigne and Yimin Zou*. Anterior turning of commissural axons after midline crossing guided by Wnt/Frizzled signaling. Science. 2003. 302: 1984-8. Yaobo Liu, Jun Shi, Chin-Chun Lu, Zheng-Bei Wang, Xuejun Song and Yimin Zou*. Anterior-posterior guidance of corticospinal tract axons by conserved repulsive Wnt-Ryk interaction. Nature Neuroscience. 2005. 8(9):1151-9. Lee Fradkin, Gian Garriga , Patricia C. Salinas, John Thomas, Xiang Yu and Yimin Zou. Wnt signaling in neural circuit development (minireview). Journal of Neuroscience. November 9, 2005. 25(45):10376-10378. Adam Schmitt, Jun Shi, Alex Wolf, Chin-Chun Lu, Leslie A. King and Yimin Zou. Wnt-Ryk signaling mediates medial-lateral retinotectal topographic mapping. Nature (Article). Advanced Online Publication November 9, 2005. Doi:10.1038/nature04334. Yimin Zou. Navigating the anterior-posterior axis with Wnts (preview). Neuron. 2006 Mar 16;49(6):787-9. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||