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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
1. Alex Kolodkin



Department of Neuroscience

Johns Hopkins University

Molecular Mechanisms of Neuronal Growth Cone Guidance

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


Université Paris 6


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

Mechanisms to promote axonal regeneration in vivo.

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


Wnt signaling in nervous system wiring

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.


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


DATE OF BIRTH December 24, 1957
PLACE OF BIRTH Queens, New York


Ph.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


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

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
Study Sections: NIH: MCDN1-SEP: 9/98; NIDCR-SEP: 4/00; NIDCR-SEP: 6/00; NINDS-SEP:3/01; NIDCR-SEP:5/01; ZRG1-SEP: 3/02; ZRG1-SEP: 7/02; BRB-SSEP: 3/04; MDCN-5-SEP(Chairperson for meeting):8/03; MCDN-1 (ad hoc):10/03; ZRG1-MCDN-A SEP: 7/04; NDPR (ad hoc): 6/05, 10/05

OTHER: NY State Spinal Cord Injury Research Study Sections: 9/00; 5/01; Christopher Reeve PF: 9/04; 9/05.
Editorial Activites: Neuron, Advisory Board, 1/00–present; Journal of Neuroscience, Advisory Board, 2005–present; Molecular and Cellular Neuroscience, Associate Editor, 2005–present (additional manuscript reviews for many journals including: Cell, Nature, Science, Development, Nature Neurosci., etc.)
Scientific Advisory Boards: The Christopher Reeve Paralysis Foundation: 1/05-present; The Robert Packard Center for ALS Research at Johns Hopkins: 5/03-present; New York State Spinal Cord Injury Research Board Scientific Advisory Committee: 1/00–12/02
Grant Reviews: NSF-primary grant reviews; The Welcome Trust; MRC (London); Science Foundation Ireland; Spinal Cord Research Foundation of the PVA; Der Wissenschaftsfond (FWF), Austria; Biomedical Research Council of Singapore; EPSCR/Puerto Rico; Allegheny University of the Health Sciences/Intramural Grant Program; MBRS-SCORE/U. Puerto Rico
Miscellaneous: Chair, Semaphorin Nomenclature Committee (5/99); Consultant: SmithKline Beecham (1/98-1/00); NIMH/NIDA: Consultant on Molecular Anatomy Mouse Brain Atlas Database (8/00); NIH/NINDS: Workshop on “Spinal Cord Repair” (1/01); NIMH/NIDA Workshop on “Setting Priorities for Molecular Neuroanatomy in the Post-Genomic Era” (1/02)
Meeting Organizer: Cold Spring Harbor, Neurobiology of Drosophila, Sept. 2007; EMBO workshop on “Semaphorin Function and Mechanisms of Action: A decade of Semaphorin Research,” June, 2003, Corsica, France

Selected 5 publications:
Huber, A.B., Kania, A., Tran, T.S., Gu, C., de Marco-Garcia, N., Lieberam, I., Johnson, D., Jessell, T.M., 1Ginty, D.D., 1Kolodkin. A.L. (2005). Semaphorin-neuropilin signaling mediates distinct aspects of spinal motor axon guidance. Neuron, in press.

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.
Pasterkamp, R.J., Peshon, J.J., Spriggs, M.K. and Kolodkin, A.L.. (2003). Semaphorin 7A promotes axon outgrowth through integrins and MAPKs. Nature 424, 398-405.

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).

CNRS UMR 7102Université Paris 6,Batiment B, pièce 611,
Case 12, 9 Quai Saint Bernard,75005 Paris, France

tel: +33-144273447/144272130, fax: +33-144272669; e-mail:

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.

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.

Marie T. Filbin. Ph.D.,

Distinguished Professor



(if applicable)



University of Bath, England




University of Bath, England




University of Maryland



John Hopkins University




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.
Advisory Boards:

• 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


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







Postdoctoral Fellow



Developmental Neuroscience

University of California, San Francisco, HHMI



Biochemistry and Molecular Biology

University of California, Davis and San Diego




Fudan University, Shanghai, China

Research Experience

05/06-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.
11/00 – 04/06: Assistant Professor, 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.

12/96-10/00: Postdoctoral Fellow, University of California, San


Molecular mechanisms of axon guidance. Midline

pathfinding of commissural axons. Signaling mechanisms of

chemorepulsive guidance. Advisor: Dr. Marc Tessier-

01/96-11/96: Postdoctoral Research, University of California, San Diego. Characterization of a cardiac-specific ankyrin-repeat protein (CARP) in mammalian cardiac muscle development. Advisor: Dr. Kenneth R. Chien.

09/92-12/95: Doctoral Dissertation at the University of California, San


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.
01/88-06/89: Undergraduate Thesis Research in Genetics,

Fudan University, Shanghai, China. Eucaryotic gene


Advisor: Professor Shou-Yuan Zhao.

Honors and Awards

2003 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


Yimin 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.

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