Department of Cell Morphology and Molecular Neurobiology

Prof. Dr. Stefan Wiese

A major interest of the Research group for Molecular Cell Biology is the analysis of pathomechanisms leading to motoneuron cell death or axonal degeneration. In the past years the research focus has been on the different signalling cascades that are potentially involved in these mechanisms. During this work, key regulator proteins in the mechanisms of motoneuron survival have been identified and new insights into protein-protein interactions have been described. Especially the intracellular signalling cascades for the Ras/Raf/MAPK and the PI3K/Akt are of great interest. The group has great expertise in the culture systems of embryonic mouse motoneurons, sensory neurons, astrocytes and neural stem cells from embryonic forebrain and spinal cord as well as in the culture of several cell lines as models for neuron and glia differentiation. Motoneuron cultures have also been performed from different species including chick and rat. Intensive studies have been performed on the survival and cell death of cultured motoneurons and sensory neurons in chicken and various mouse mutants to define the role of the different proteins in the concert of survival and cell death signalling for motoneurons. Additionally the group performed analyses of neural stem cells in the context of the role of the Extracellular matrix. Here the role of Tenascin-c and modulation of sulfation and glycosaminoglycan chains in the context of proliferation and differentiation of spinal cord neural stem cells has been investigated.

Publications

• Thöne J, Ellrichmann G, Seubert S, Peruga I, Lee DH, Conrad R, Hayardeny L, Comi G, Wiese S, Linker RA, Gold R. Modulation of autoimmune demyelination by laquinimod via induction of brain-derived neurotrophic factor. Am J Pathol. 2012 Jan;180(1):267-74.
• Gorboulev V, Schürmann A, Vallon V, Kipp H, Jaschke A, Klessen D, Friedrich A, Scherneck S, Rieg T, Cunard R, Veyhl-Wichmann M, Srinivasan A, Balen D, Breljak D, Rexhepaj R, Parker HE, Gribble FM, Reimann F, Lang F, Wiese S, Sabolic I, Sendtner M, Koepsell H. Na(+)-D-glucose cotransporter SGLT1 is pivotal for intestinal glucose absorption and glucose-dependent incretin secretion. Diabetes. 2012 Jan;61(1):187-96.
• Conrad R, Jablonka S, Sczepan T, Sendtner M, Wiese S, Klausmeyer A. Lectin-based isolation and culture of mouse embryonic motoneurons. J Vis Exp. 2011 Sep 15;(55).
• Linker RA, Lee DH, Ryan S, van Dam AM, Conrad R, Bista P, Zeng W, Hronowsky X, Buko A, Chollate S, Ellrichmann G, Brück W, Dawson K, Goelz S, Wiese S, Scannevin RH, Lukashev M, Gold R. Fumaric acid esters exert neuroprotective effects in neuroinflammation via activation of the Nrf2 antioxidant pathway. Brain. 2011 Mar;134(Pt 3):678-92.
• Klausmeyer A, Conrad R, Faissner A, Wiese S. Influence of glial-derived matrix molecules, especially chondroitin sulfates, on neurite growth and survival of cultured mouse embryonic motoneurons. J Neurosci Res. 2011 Feb;89(2):127-41.
• Linker RA, Lee D, Demir S, Wiese S, Kruse N, Siglienti I, Gerhardt E, Neumann H, Sendtner M, Lühder F, Gold R. (2010) Functional role of brain-derived neurotrophic factor in neuroprotective autoimmunity: therapeutic implications in a model of multiple sclerosis. Brain Aug; 133: 2248-2263.
• Rauskolb S, Zagrebelsky M, Dreznjak A, Deogracias R, Matsumoto T, Wiese S, Erne B, Sendtner M, Schaeren-Wiemers N, Korte M, Barde YA. (2010) Global deprivation of brain-derived neurotrophic factor in the CNS reveals an area-specific requirement for dendritic growth. J Neurosci. Feb 3;30(5):1739-49.
• Wiese S, Herrmann T, Drepper C, Jablonka S, Funk N, Klausmeyer A, Rogers ML, Rush R, Sendtner M. (2010) Isolation and enrichment of embryonic mouse motoneurons from the lumbar spinal cord of individual mouse embryos. Nat Protoc. ;5(1):31-8.
• Strelau J, Strzelczyk A, Rusu P, Bendner G, Wiese S, Diella F, Altick AL, von Bartheld CS, Klein R, Sendtner M, Unsicker K. (2009) Progressive postnatal motoneuron loss in mice lacking GDF-15. J Neurosci. Oct 28;29(43):13640-8.
• Trimbuch T, Beed P, Vogt J, Schuchmann S, Maier N, Kintscher M, Breustedt J, Schuelke M, Streu N, Kieselmann O, Brunk I, Laube G, Strauss U, Battefeld A, Wende H, Birchmeier C, Wiese S, Sendtner M, Kawabe H, Kishimoto-Suga M, Brose N, Baumgart J, Geist B, Aoki J, Savaskan NE, Bräuer AU, Chun J, Ninnemann O, Schmitz D, Nitsch R. (2009) Synaptic PRG-1 modulates excitatory transmission via lipid phosphate-mediated signaling. Cell. Sep 18;138(6):1222-35.
• Wiese S, Jablonka S, Holtmann B, Orel N, Rajagopal R, Chao MV, Sendtner M. Adenosine receptor A2A-R contributes to motoneuron survival by transactivating the tyrosine kinase receptor TrkB. Proc Natl Acad Sci U S A. 2007 Oct 23;104(43):17210-5.
• Frebel K, Wiese S, Funk N, Sendtner M. Differential Modulation of Neurite Growth by the S- and the L-Forms of bag1, a Co-Chaperone of Hsp70. Neurodegener Dis. 2007;4(2-3):261-9.
• Fischer A, Hekman M, Kuhlmann J, Rubio I, Wiese S, Rapp UR. B- and C-RAF display essential differences in their binding to Ras: the isotype-specific N terminus of B-RAF facilitates Ras binding. J Biol Chem. 2007 Sep 7;282(36):26503-16.
• Frebel K, Wiese S. Signalling molecules essential for neuronal survival and differentiation.Biochem Soc Trans. 2006 Dec;34(Pt 6):1287-90. Review.
• Camarero G, Tyrsin OY, Xiang C, Pfeiffer V, Pleiser S, Wiese S, Gotz R, Rapp UR. Cortical migration defects in mice expressing A-RAF from the B-RAF locus. Mol Cell Biol. 2006 Oct;26(19):7103-15.
• Ito Y, Wiese S, Funk N, Chittka A, Rossoll W, Bommel H, Watabe K, Wegner M, Sendtner M. Sox10 regulates ciliary neurotrophic factor gene expression in Schwann cells. Proc Natl Acad Sci U S A. 2006 May 16;103(20):7871-6.
• Hekman M, Albert S, Galmiche A, Rennefahrt UE, Fueller J, Fischer A, Puehringer D, Wiese S, Rapp UR. Reversible membrane interaction of BAD requires two C-terminal lipid binding domains in conjunction with 14-3-3 protein binding. J Biol Chem. 2006 Jun 23;281(25):17321-36.
• Götz R, Wiese S, Takayama S, Camarero GC, Rossoll W, Schweizer U, Troppmair J, Jablonka S, Holtmann B, Reed JC, Rapp UR, Sendtner M. Bag1 is essential for differentiation and survival of hematopoietic and neuronal cells. Nat Neurosci. 2005 Sep;8(9):1169-78.
• Mees A, Rock R, Ciccarelli FD, Leberfinger CB, Borawski JM, Bork P, Wiese S, Gessler M, Kerkhoff E. Very-KIND is a novel nervous system specific guanine nucleotide exchange factor for Ras GTPases. Gene Expr Patterns. 2005 Dec;6(1):79-85.
• Holtmann B, Wiese S, Samsam M, Grohmann K, Pennica D, Martini R, Sendtner M. Triple knock-out of CNTF, LIF, and CT-1 defines cooperative and distinct roles of these neurotrophic factors for motoneuron maintenance and function. J Neurosci. 2005 Feb 16;25(7):1778-87.
• Banks GB, Kanjhan R, Wiese S, Kneussel M, Wong LM, O'Sullivan G, Sendtner M, Bellingham MC, Betz H, Noakes PG. Glycinergic and GABAergic synaptic activity differentially regulate motoneuron survival and skeletal muscle innervation. J Neurosci. 2005 Feb 2;25(5):1249-59.
  Erratum in: J Neurosci. 2005 Mar 16;25(11):3018-21.
• Wiese S, Beck M, Karch C, Sendtner M. Signalling mechanisms for survival of lesioned motoneurons. Acta Neurochir Suppl. 2004; 89:21-35. Review.
• Harder F, Kirchhof N, Petrovic S, Wiese S, Muller AM. Erythroid-like cells from neural stem cells injected into blastocysts. Exp Hematol. 2004 Jul;32(7):673-82.
• Jablonka S, Wiese S, Sendtner M. Axonal defects in mouse models of motoneuron disease. J Neurobiol. 2004 Feb 5;58(2):272-86.
• Hekman M, Wiese S, Metz R, Albert S, Troppmair J, Nickel J, Sendtner M, Rapp UR. Dynamic changes in C-Raf phosphorylation and 14-3-3 protein binding in response to growth factor stimulation: differential roles of 14-3-3 protein binding sites. J Biol Chem. 2004 Apr 2;279(14):14074-86.
• Bömmel H, Xie G, Rossoll W, Wiese S, Jablonka S, Boehm T, Sendtner M. Missense mutation in the tubulin-specific chaperone E (Tbce) gene in the mouse mutant progressive motor neuronopathy, a model of human motoneuron disease. J Cell Biol. 2002 Nov 25;159(4):563-9.
• Mäurer M, Loserth S, Kolb-Maurer A, Ponath A, Wiese S, Kruse N, Rieckmann P. A polymorphism in the human cytotoxic T-lymphocyte antigen 4 ( CTLA4) gene (exon 1 +49) alters T-cell activation. Immunogenetics. 2002 Apr;54(1):1-8.
• Schweizer U, Gunnersen J, Karch C, Wiese S, Holtmann B, Takeda K, Akira S,
• Sendtner M. Conditional gene ablation of Stat3 reveals differential signaling requirements for survival of motoneurons during development and after nerve injury in the adult. J Cell Biol. 2002 Jan 21;156(2):287-97.
• Beck M, Karch C, Wiese S, Sendtner M. Motoneuron cell death and neurotrophic factors: basic models for development of new therapeutic strategies in ALS. Amyotroph Lateral Scler Other Motor Neuron Disord. 2001 Mar;2 Suppl 1:S55-68. Review.
• Jablonka S, Bandilla M, Wiese S, Buhler D, Wirth B, Sendtner M, Fischer U. Co-regulation of survival of motor neuron (SMN) protein and its interactor SIP1 during development and in spinal muscular atrophy. Hum Mol Genet. 2001 Mar 1;10(5):497-505.
• Wiese S, Pei G, Karch C, Troppmair J, Holtmann B, Rapp UR, Sendtner M. Specific function of B-Raf in mediating survival of embryonic motoneurons and sensory neurons. Nat Neurosci. 2001 Feb;4(2):137-42.
• Oppenheim RW, Wiese S, Prevette D, Armanini M, Wang S, Houenou LJ, Holtmann B, Gotz R, Pennica D, Sendtner M. Cardiotrophin-1, a muscle-derived cytokine, is required for the survival of subpopulations of developing motoneurons. J Neurosci. 2001 Feb 15;21(4):1283-91.

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