====== Lynn Landmesser, Ph.D. ====== #template(faculty_profile.php|... * FName: Lynn * LName: Landmesser * Degree: Ph.D. * Picture: lynn_photo2_color_correct_scaled.jpg * Position: Arline J. & Curtis F. Garvin Professor \\ Member of NAS \\ Chair of Department of Neurosciences * Organization: Case Western Reserve University * Address_1: School of Medicine, Room E653 * Address_2: 10900 Euclid Ave * Address_3: Cleveland OH, 44106-4975 * Phone: (216) 368-3996 * Fax: (216) 368-4650 * Email: lynn.landmesser@case.edu * PubMed_Search: Landmesser LT + Case Western )# ===== RESEARCH INTERESTS ===== We are interested in understanding the cellular and molecular mechanisms responsible for the formation of spinal motor circuits in vertebrates; the phenomena studied include mechanisms of motor axon pathfinding, the formation of functionally effective synapses, the assembly of motor- and interneurons into locomotor circuits, and the role of spontaneous rhythmic electrical activity in these processes. We believe that the mechanisms used during development to assemble the nervous system will be relevant to strategies for restoring neural circuits that have been damaged by injury or disease. Using embryonic mouse and avian spinal cords as models, the laboratory applies a wide range of techniques including electrophysiology and Ca2+ imaging of isolated spinal cord preparations or cord slices, molecular approaches to alter the expression of molecules in-vivo or in motoneuron-myotube cell cultures, specific tract tracing, dynamic imaging of fluorescently labeled cells, and biochemistry. By combining electrophysiology and imaging of synaptic vesicle cycling at mouse neuromuscular junctions we recently discovered that different isoforms of NCAM play distinct and essential roles in both synaptic maturation and in maintaining effective transmission when adult junctions are activated repetitively. A specific domain on NCAM 180 is needed to activate an activity dependent signaling pathway, involving MLCK and myosin II, which is required to rapidly replenish synaptic vesicles during high frequency stimulation. We are now using bioinformatic, molecular, and physiological approaches to further decipher this pathway as well as a frequency dependent switch in the mode of synaptic vesicle cycling. The role of NCAM isoforms (and other molecules such as CD24) in the selective targeting of transmitter release machinery to synapses is being studied in motoneuron-myotube cultures in which one or more isoforms is selectively expressed pre- or post-synaptically. We believe that these observations are relevant to other parts of the nervous system as NCAM null mice also exhibit impaired secretion of adrenalin from chromaffin cells, and defects in hippocampal LTP, learning, and memory. A second area of interest is to understand the role that rhythmic spontaneous activity, which is widespread throughout the developing nervous system, plays in the development of spinal motor circuits. By elucidating the transmitters and circuit that drives this activity we were able to alter it during precise periods of chick embryo development via in-ovo drug application. We made the surprising discovery that modest alterations in the frequency of this activity, as axons were growing to their targets, caused either dorsal-ventral or motoneuron pool-specific axon pathfinding errors depending on the sign of the alteration. We are now using channels that can be activated by light to drive activity in intact developing embryos with different stimulus patterns to elucidate downstream signaling pathways responsible for these pathfinding errors. By altering activity even earlier and by using 2-photon Ca2+ imaging to asses the alterations, we will test whether the generation and phenotypic differentiation of specific subtypes of motor- and intern-neurons and their assembly into circuits is sensitive to activity. Our observations show that any maternally taken drugs, which affect such early activity, have the potential to cause defects in the formation of spinal cord circuits. ===== SELECTED PUBLICATIONS ===== #template?key=Landmesser(dokudata.php|... * Author: Kariya S., Park G.H., Maeno-Hikichi Y., Leykekhman O., Lutz C., Arkovitz, M.S., Landmesser, L.T., Monani, U.R. * Title: Reduced SMN protein impairs maturation of the neuromuscular junctions in mouse models of spinal muscular atrophy. * Journal: Hum. Mol. Genet. * Year: 2008 * Selected: true ---- * Author: Hanson MG, Milner LD, Landmesser LT. * Title: Spontaneous rhythmic activity in early chick spinal cord influences distinct motor axon pathfinding decision. * Journal: Brain Research Reviews * Year: 2008 * SerialDate: 20070000 * Selected: true * Student: true * Pages: 77-85 * Volume: 57 * Selected: true ---- * Author: Hata, K., Polo-Parada, L., and Landmesser, L.T. * Title: Selective targeting of different Neural cell adhesion molecule isoforms during motoneuron-myotube synapse formation in culture and the switch from an immature to mature form of synaptic vesicle cycling * Journal: J. Neurosci. * Year: 2007 * Pages: 14481-14493 * Volume: 27 * Selected: true ---- * Author: Hanson MG, Landmesser LT. * Title: Increasing the frequency of spontaneous rhythmic activity disrupts pool-specific axon fasciculation and pathfinding of embryonic spinal motoneurons. * Year: 2006 * Date: 2006 Dec 6 * SerialDate: 20061206 * Journal: J. Neurosci. * Volume: 26 * Issue: 49 * Pages: 12769-80 * Selected: true * Student: true ---- * ID: 16306259 * Author: Li X, Gutierrez DV, Hanson MG, Han J, Mark MD, Chiel H, Hegemann P, Landmesser LT, Herlitze S. * Title: Fast noninvasive activation and inhibition of neural and network activity by vertebrate rhodopsin and green algae channelrhodopsin. * Journal: Proc Natl Acad Sci U S A. * Year: 2005 * Date: 2005 Dec * Volume: 6 * Issue: 102(49) * Pages: 17816-17821 * Status: Epub 2005 Nov 23 * Selected: true ---- * ID: 15953420 * Author: Polo-Parada L, Plattner F, Bose C, Landmesser LT. * Volume: 46 * Issue: 6 * Year: 2005 * Date: 2005 Jun 16 * Journal: Neuron * Pages: 917-931 * Title: NCAM 180 acting via a conserved C-terminal domain and MLCK is essential for effective transmission with repetitive stimulation. * Selected: true * Postdoc: true ---- * ID: 15800072 * Author: Chan SA, Polo-Parada L, Landmesser LT, Smith C. * Volume: 94 * Issue: 2 * Year: 2005 * Date: 2005 Aug * Journal: J Neurophysiol * Pages: 1037-1047 * Title: Adrenal chromaffin cells exhibit impaired granule trafficking in NCAM knockout mice. * Status: 2005/03/30 [aheadofprint] * Selected: true ---- * ID: 15339650 * Author: Hanson MG, Landmesser LT. * Volume: 43 * Issue: 5 * Year: 2004 * Date: 2004 Sep 2 * Journal: Neuron * Pages: 687-701 * Title: Normal patterns of spontaneous activity are required for correct motor axon guidance and the expression of specific guidance molecules. * Selected: true * Student: true ---- * ID: 14985425 * Author: Polo-Parada L, Bose CM, Plattner F, Landmesser LT. * Volume: 24 * Issue: 8 * Year: 2004 * Date: 2004 Feb 25 * Journal: J Neurosci * Pages: 1852-1864 * Title: Distinct roles of different neural cell adhesion molecule (NCAM) isoforms in synaptic maturation revealed by analysis of NCAM 180 kDa isoform-deficient mice. * Selected: true * Postdoc: true ---- * ID: 12533619 * Author: Hanson MG, Landmesser LT. * Volume: 23 * Issue: 2 * Year: 2003 * Date: 2003 Jan 15 * Journal: J Neurosci * Pages: 587-600 * Title: Characterization of the circuits that generate spontaneous episodes of activity in the early embryonic mouse spinal cord. * Selected: true * Student: true ---- * ID: 11738028 * Author: Polo-Parada L, Bose CM, Landmesser LT. * Volume: 32 * Issue: 5 * Year: 2001 * Date: 2001 Dec 6 * Journal: Neuron * Pages: 815-828 * Title: Alterations in transmission, vesicle dynamics, and transmitter release machinery at NCAM-deficient neuromuscular junctions. * Selected: true * Postdoc: true ---- * ID: 11255031 * Author: Landmesser LT. * Volume: 19 * Issue: 2 * Year: 2001 * Date: 2001 Apr * Journal: Int J Dev Neurosci * Pages: 175-182 * Title: The acquisition of motoneuron subtype identity and motor circuit formation. * Selected: true ---- * ID: 10964958 * Author: Rafuse VF, Polo-Parada L, Landmesser LT. * Volume: 20 * Issue: 17 * Year: 2000 * Date: 2000 Sep 1 * Journal: J Neurosci * Pages: 6529-6539 * Title: Structural and functional alterations of neuromuscular junctions in NCAM-deficient mice. * Selected: false * Postdoc: true ---- * ID: 10648711 * Author: Rafuse VF, Landmesser LT. * Volume: 20 * Issue: 3 * Year: 2000 * Date: 2000 Feb 1 * Journal: J Neurosci * Pages: 1056-1065 * Title: The pattern of avian intramuscular nerve branching is determined by the innervating motoneuron and its level of polysialic acid. * Selected: true * Postdoc: true ---- * ID: 10479694 * Author: Usiak MF, Landmesser LT. * Volume: 19 * Issue: 18 * Year: 1999 * Date: 1999 Sep 15 * Journal: J Neurosci * Pages: 7925-7939 * Title: Neuromuscular activity blockade induced by muscimol and d-tubocurarine differentially affects the survival of embryonic chick motoneurons. * Selected: false * Student: true ---- * ID: 10191318 * Author: Milner LD, Landmesser LT. * Volume: 19 * Issue: 8 * Year: 1999 * Date: 1999 Apr 15 * Journal: J Neurosci * Pages: 3007-3022 * Title: Cholinergic and GABAergic inputs drive patterned spontaneous motoneuron activity before target contact. * Selected: true * Student: true ---- * ID: 9707397 * Author: Landmesser LT. * Volume: 8 * Issue: 16 * Year: 1998 * Date: 1998 Jul 30-Aug 13 * Journal: Curr Biol * Pages: R564-R567 * Title: Synaptic plasticity: keeping synapses under control. * Selected: false ---- * ID: 9547238 * Author: Milner LD, Rafuse VF, Landmesser LT. * Volume: 18 * Issue: 9 * Year: 1998 * Date: 1998 May 1 * Journal: J Neurosci * Pages: 3297-3313 * Title: Selective fasciculation and divergent pathfinding decisions of embryonic chick motor axons projecting to fast and slow muscle regions. * Selected: true * Student: true ---- * ID: Book-001 * Author: Stoeckli ET, Landmesser LT. * Year: 1998 * Chapter: Molecular mechanisms of growth cone guidance in the vertebrate nervous system. * Title: In Immunoglobulin superfamily adhesion molecules in neural development, regeneration, and disease. * Pages: pp. 161-181 * Publisher: Ed. P. Sonderegger, Harwood Academic Pub. * Postdoc: true ---- * ID: Review-001 * Author: Stoeckli ET, Landmesser LT. * Volume: 8 * Issue: 1 * Year: 1998 * Date: 1998 Feb * Journal: Curr Opin Neurobiol * Pages: 73-79 * Title: Axon guidance at choice points. * Status: Review * Selected: false * Postdoc: true ---- * ID: 9052792 * Author: Stoeckli ET, Sonderegger P, Pollerberg GE, Landmesser LT. * Volume: 18 * Issue: 2 * Year: 1997 * Date: 1997 Feb * Journal: Neuron * Pages: 209-221 * Title: Interference with axonin-1 and NrCAM interactions unmasks a floor-plate activity inhibitory for commissural axons. * Selected: true ---- * ID: 8824325 * Author: Rafuse VF, Milner LD, Landmesser LT. * Volume: 16 * Issue: 21 * Year: 1996 * Date: 1996 Nov 1 * Journal: J Neurosci * Pages: 6864-6877 * Title: Selective innervation of fast and slow muscle regions during early chick neuromuscular development. * Selected: false ---- * ID: 7541632 * Author: Stoeckli ET, Landmesser LT. * Volume: 14 * Issue: 6 * Year: 1995 * Date: 1995 Jun * Journal: Neuron * Pages: 1165-1179 * Title: Axonin-1, Nr-CAM, and Ng-CAM play different roles in the in vivo guidance of chick commissural neurons. * Selected: false )# #template?query=Selected&key=Landmesser(publications.php|...)# ===== STUDENT FIRST AUTHOR PUBLICATIONS ===== #template?query=Student&key=Landmesser(publications.php|...)# ===== POSTDOC FIRST AUTHOR PUBLICATIONS ===== #template?query=Postdoc&key=Landmesser(publications.php|...)# #template?key=Landmesser(dokudata.php|...)# (space) ===== STUDENT JOB PLACEMENT ===== #template(current_positions.php|... * Title: Ph.D. Student ---- * Name: Sheryl Scott * Position: Professor, Dept. of Neuroscience, Univ. of Utah ---- * Name: Deborah Morris * Position: Physician, practicing in Boston area ---- * Name: Marcia Honig * Position: Prof., Dept. of Anatomy & Neurobio., Univ. of TN ---- * Name: Michael Vogel * Position: Assoc. Prof., Dept. of Psychiatry, Univ. of Maryland ---- * Name: Lisa Dahm * Position: Director, Research Computer Services, Beckman Research Inst., City of Hope, CA ---- * Name: **Jicheng Tang** * Position: **Assistant Professor, Dept. of Psychiatry, Cornell Univ.School of Med.** ---- * Name: **Fabiana Kupke** * Position: **Res. Assoc., University of Aukland, New Zeland** ---- * Name: **Louise Milner** * Position: **Resident, Dept. Radiology, Wake Forest Univ.** ---- * Name: **M. Gartz Hanson** * Position: **Research Assoc. Univ. of Colorado Health Sciences Center** )# (space) ===== POSTDOC AND RESEARCH ASSOCIATES JOB PLACEMENT ===== #template(current_positions.php|... * Title: Postdoc / RA ---- * Name: Cynthia Lance-Jones * Position: Prof., Dept. of Neurobio. & Anatomy, Univ. of Pittsburgh, S.O.M. ---- * Name: Michael O'Donovan * Position: Position: Sr. Scientist, National Inst. of Neurological Disorders and Stroke ---- * Name: Kathryn Tosney * Position: Chair, Dept. of Biology, Univ. of Miami ---- * Name: Hideaki Tanaka * Position: Prof., Dept. of Pharmacology, Gunma Univ., Japan ---- * Name: **Esther Stoeckli** * Position: **Assoc. Prof., University of Zurich, Switzerland** ---- * Name: **Victor Rafuse** * Position: **Prof., Dept. of Pharmacology, Dalhousie Univ, Canada** ---- * Name: **Shilpi Banerjee** * Position: **Patent law - Fish and Neave, NYC** ---- * Name: **Luis Polo-Parada** * Position: **Asst. Prof., Dept. of Medical Pharmacology and Physiology, University of Missouri** )# (space) ~~NOTOC~~