of the Max - MDC

More documents

Recommendations

Info

Genetic Analysis of Neural Circuits Alistair N. Garratt (Helmholtz Fellow) We employ mice as model systems to characterize the role of specific genes in neural circuits through classical and conditional (tissue-specific) gene inactivation. Nociceptive tuning by the receptor tyrosine kinase c-Kit Christina Frahm, Carola Griffel The molecular mechanisms regulating the sensitivity of sensory circuits to environmental stimuli are still poorly understood. We have discovered a central role for Stem Cell Factor (SCF) and its receptor, c-Kit, in tuning the responsiveness of sensory neurons to natural stimuli. For this, we have performed the first analysis of nervous system phenotypes in mice lacking a functional SCF/c-Kit signaling system. We employed c-Kit mutants in which the lethal anemia had been rescued by an erythropoietin-transgene. C-Kit mutant mice displayed profound thermal hypoalgesia, attributable to a marked elevation in the thermal threshold and reduction in spiking rate of polymodal heat-sensitive C-fiber nociceptors (in collaboration with Gary Lewin, MDC). Acute activation of c- Kit by its ligand, SCF, resulted in a reduced thermal threshold and profound potentiation of heat-activated currents in isolated small diameter neurons, and thermal hyperalgesia in mice. SCF induced thermal hyperalgesia required the TRP-family cation channel TRPV1. In addition, lack of c-Kit signaling during development resulted in hypersensitivity of discrete mechanoreceptive neuronal subtypes to mechanical stimulation. Thus c-Kit, can be now be grouped into a small family of receptor tyrosine kinases, including c-Ret and TrkA, that control the transduction properties of distinct types of sensory neuron to thermal and mechanical stimuli. Roles of the Teashirt genes in neural circuits Elena Rocca, Carola Griffel We initially identified the Teashirt genes, encoding zinc homeodomain transcription factors, together with c-Kit, in a screen of gene expression in the substantia gelatinosa, an area of particular importance for the reception of pain stimuli. We have since generated knock-out mice for Tshz1 andTshz2 and conditional alleles for Tshz1 and Tshz3. Analyses of spinal cord phenotypes in Tshz1 mutants indicated redundancy in gene function with other Tshz genes expressed in overlapping neuronal populations. We have recently identified, however, a function of Tshz1 in the olfactory bulb. The early development of the olfactory bulb is still poorly understood, and many efforts have instead been focussed on molecular analysis of the neurogenesis that occurs in this structure throughout adult life. Our analyses at present indicate that Tshz1 controls the development of an early emigrating population of granule cell interneurons that occupy the outer layer of the granule cell layer in the maturing olfactory bulb. Analyses of cell proliferation indicate that these cells are generated in the rostral telencephalon already at E11.5-E12.5, and emigrate soon after into the developing olfactory bulb. One short-term aim is to determine the role of Tshz1 in the specification, proliferation and/or migration of this early emigrating neuronal population in embryonic development. Preliminary studies indicate that mutant cells clump together and fail to distribute radially within the olfactory bulb, a phenotype associated with changes in Semaphorin signalling (identified by microarray analysis). Interestingly, Tshz1 remains expressed in the subventricular zone of the adult brain, the site where continuous adult neurogenesis occurs to generate interneurons destined to migrate into the olfactory bulb. In the longer term, therefore, we will extend the analyses of Tshz1 function to postnatal and adult neurogenesis, using the conditional allele to circumvent the embryonic lethality that occurs in the classical loss-of-function mutants. Selected Publications Milenkovic, N, Frahm, C, Gassmann, M, Griffel, C, Erdmann, B, Birchmeier, C, Lewin, GR, Garratt, AN. (2007). Nociceptive tuning by Stem Cell Factor/c-Kit signaling. Neuron, in press. Grego-Bessa, J, Luna-Zurita, L, del Monte, G, Bolós, V, Melgar, P, Arandilla, A, Garratt, AN, Zang, H, Mukouyama, Y, Chen, H, Shou, W, Ballestar, E, Esteller, M, Rojas, A, Pérez-Pomares, de la Pompa, JL. (2007). Notch signalling is essential for cardiac ventricular chamber development. Developmental Cell 12: 415-429. Willem, M, Garratt, AN*, Novak, B, Citron, M, Kaufmann, S, Rittger, A, Saftig, P, De Strooper, B, Birchmeier, C, Haass, C.* (2006). Control of peripheral nerve myelination by the (-secretase BACE1. Science 314: 664-666 (*corresponding authors). Garratt, AN. (2006). “To erb-B or not to erb-B...” Neuregulin- 1/ErbB signaling in heart development and function. J. Mol. Cell. Cardiol. 41: 215-218. López-Bendito, G, Cautinat, A, Sánchez, JA, Bielle, F, Flames, N, Garratt, AN, Tagmale, D, Role, LW, Charnay, P, Marín, O, Garel, S. (2006). Tangential migration controls axon guidance: a role for Neuregulin-1 in thalamocortical axon navigation. Cell 125: 127-142. 158 Function and Dysfunction of the Nervous System
Structure of the Group Group Leader Dr. Alistair N. Garratt Graduate Students Christina Frahm Elena Rocca Technical Assistant Carola Griffel Figure1. A, c-Kit heterozygotes and homozygote mutants are characterized by pigmentation defects in coat colour. c-Kit-/- mice show reduced sensitivity to radiant heat applied to the paw (B, left panel), and heightened sensitivity to a small diameter mechanical probe (B, right panel). Figure 2. Tshz1 mutants (B) lack an outer ring of GABA-ergic granule cell neurons of the olfactory bulb, here marked with an RNA probe against glutamic acid decarboxylase (GAD67). Atanasoski, S, Scherer, S, Sirkowski, E, Leone, D, Garratt, AN, Birchmeier C, Suter U. (2006). ErbB2 signaling in Schwann cells is largely dispensable for maintenance of myelinated peripheral nerves and proliferation of adult Schwann Cells following injury. J. Neurosci. 26: 2124-2131. Humphries, JD, Schofield, NR, Mostafavi-Pour, Z, Green, LJ, Garratt, AN, Mould, AP, Humphries, MJ. (2005). Dual functionality of the anti-β1 integrin antibody, 12G10, exemplifies agonistic signalling from the ligand-binding pocket of integrin adhesion receptors. J. Biol. Chem. 280: 10234-10243. Function and Dysfunction of the Nervous System 159
Page 1 and 2:
Research Report 2008 MDC Berlin-Buc
Page 3 and 4:
Research Report 2008 (covers the pe
Page 5 and 6:
Cell Polarity and Epithelial Morpho
Page 7 and 8:
Molecular Cell Biology and Gene The
Page 9 and 10:
Foreword Vorwort As this book was b
Page 11 and 12:
which survey the quality of protein
Page 13 and 14:
Two major grants from the Helmholtz
Page 15 and 16:
Cardiovascular and Metabolic Diseas
Page 17 and 18:
ing on this topic have made importa
Page 19 and 20:
explain why a certain gene or seque
Page 21 and 22:
Figure 2. Uptake of lipoprotein (A)
Page 23 and 24:
Molecular Mechanisms in Embryonic F
Page 25 and 26:
Cardiovascular Hormones Michael Bad
Page 27 and 28:
Angiogenesis and Cardiovascular Pat
Page 29 and 30:
Hypertension, Vascular Disease, Gen
Page 31 and 32:
Structure of the Group Group Leader
Page 33 and 34:
Page 35 and 36:
eceptors did not change. Thus, syst
Page 37 and 38:
Mechanisms of Hypertensioninduced T
Page 39 and 40:
Differentiation and Regeneration of
Page 41 and 42:
Heart Diseases Coordinator: Ludwig
Page 43 and 44:
Page 45 and 46:
Page 47 and 48:
Page 49 and 50:
Page 51 and 52:
Page 53 and 54:
Figure 1. 3D-model of the actomyosi
Page 55 and 56:
Cell Polarity and Epithelial Morpho
Page 57 and 58:
Molecular and Cell Biology of the (
Page 59 and 60:
Page 61 and 62:
Page 63 and 64:
number of circulating antibodies to
Page 65 and 66:
Genetics, Genomics, Bioinformatics,
Page 67 and 68:
Physiology and Pathology of Ion Tra
Page 69 and 70:
Technical Assistants Alexander Fast
Page 71 and 72:
Page 73 and 74:
Page 75 and 76:
Page 77 and 78:
Page 79 and 80:
Cancer Research Krebsforschung Coor
Page 81 and 82:
how they infiltrate surrounding tis
Page 83 and 84:
(Photo: David Ausserhofer/Copyright
Page 85 and 86:
degradation (ERAD) pathway. In the
Page 87 and 88:
Structural and Functional Genomics
Page 89 and 90:
ated with the deregulation of cell
Page 91 and 92:
A B C Only functional Met keratinoc
Page 93 and 94:
I) Conditional ablation of the Bmp
Page 95 and 96:
Genetics of Tumor Progression and M
Page 97 and 98:
Signaling Mechanisms in Embryonic S
Page 99 and 100:
Surgical Oncology Peter M. Schlag O
Page 101 and 102:
Page 103 and 104:
Structure bition of differentiation
Page 105 and 106:
Page 107 and 108:
such as self-renewal and differenti
Page 109 and 110:
Signal Transduction in Tumor Cells
Page 111 and 112:
Page 113 and 114:
Page 115 and 116:
Control of DNA Replication Manfred
Page 117 and 118:
Nuclear Signalling and Chromosomal
Page 119 and 120:
Page 121 and 122: a. b. Figure 1. The Sleeping Beauty
Page 123 and 124: Structural and Functional Genomics
Page 125 and 126: A B Figure 2. Palmitoylation of the
Page 127 and 128: RNA Chemistry Eckart Matthes Hydrox
Page 129 and 130: Structure and Membrane Interaction
Page 131 and 132: Tumor Immunology Coordinator: Marti
Page 133 and 134: Formation of segregated ectopic fol
Page 135 and 136: Regulatory Mechanisms of Lymphocyte
Page 137 and 138: Biology and Targeted Therapy of Lym
Page 139 and 140: Structure of the Group Group Leader
Page 145 and 146: A Figure 1. Function of BH3-only pr
Page 147 and 148: Molecular Immunotherapy Antonio Pez
Page 149 and 150: Molecular Immunology and Gene Thera
Page 151 and 152: Molecular Cell Biology and Gene The
Page 155 and 156: A B C D CD39+ Treg cells and multip
Page 157 and 158: Experimental Pharmacology Iduna Fic
Page 161 and 162: Function and Dysfunction of the Ner
Page 163 and 164: (Photo: Dr. Hagen Wende, Research G
Page 165 and 166: tion of proteins causes human neuro
Page 167 and 168: - Pathophysiological Mechanisms of
Page 171: Stucture of the Group Group Leader
Page 175 and 176: What are the physiological features
Page 179 and 180: Visualization of the UniHi interact
Page 181 and 182: Dagmar Ehrnhöfer* Manuela Jacob* M
Page 185 and 186: Lack of axonal bifurcation within t
Page 187 and 188: Molecular Physiology of Somatic Sen
Page 189 and 190: Mitochondrial Dynamics Christiane A
Page 191 and 192: Neuronal Stem Cells Gerd Kempermann
Page 193 and 194: Targeting Ion Channel Function Ines
Page 195 and 196: RNA Editing and Hyperexcitability D
Page 197 and 198: Molecular Neurology Frauke Zipp T h
Page 201 and 202: Academics Akademische Aktivitäten
Page 203 and 204: Charité-Universitätsmedizin Berli
Page 205 and 206: Helmholtz Fellows Helmholtz-Stipend
Page 207 and 208: (Photo: Cécile Otten, Research Gro
Page 209 and 210: 2007 19. January Neujahrsempfang de
Page 211 and 212: Speaker Institute Titel of Seminar
Page 217 and 218: Overview Überblick
Page 219 and 220: erzielen, brauchen wir neue gemeins
Page 221 and 222: The Clinical Research Center (CRC)
Page 223 and 224:
y such scientists in conjunction wi
Page 225 and 226:
Zudem bietet das ECRC-Modell eine h
Page 227 and 228:
(Photo: David Ausserhofer/ Copyrigh
Page 229 and 230:
Business School” addressed challe
Page 231 and 232:
Prof. Dr. Gary R. Lewin MDC Berlin-
Page 233 and 234:
Dr. Thomas Müller Prof. Dr. Claus
Page 235 and 236:
Type of Financing/Art der Finanzier
Page 237 and 238:
Collaborative Research Centres (SFB
Page 239 and 240:
Figures for technology transfer/Ken
Page 241 and 242:
MDC MAX-DELBRÜCK-CENTRUM FÜR MOLE
Page 243 and 244:
Buschow, Christian . . . . . . . .
Page 245 and 246:
Herrmann, Ina . . . . . . . . . . .
Page 247 and 248:
Mensen, Angela . . . . . . . . . .
Page 249 and 250:
Schwarzer, Rolf . . . . . . . . . .
Page 251 and 252:
Campus Map Campusplan Robert-Rössl
Page 253 and 254:
How to find your way to the MDC Der
show all

of the Max - MDC

Create successful ePaper yourself

Delete template?

Save as template?