Research Topics
Genomes and Genes
| R KleinSummaryAffiliation: European Molecular Biology Laboratory Country: Germany Publications
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Detail Information
Publications
Bidirectional signals establish boundariesR Klein
European Molecular Biology Laboratory Meyerhofstrasse 1, 69117, Heidelberg, Germany
Curr Biol 9:R691-4. 1999..This signalling is mediated by Eph receptors and their ligands, which has been found to restrict cell intermingling in vitro...
Eph receptors and ephrins: effectors of morphogenesisN Holder
Department of Anatomy and Developmental Biology, University College, Gower Street, London, WC1 6BT, UK
Development 126:2033-44. 1999..We address the question of how the specificity of response is achieved and discuss the specificity of ephrin-Eph interactions and the significance of structural domains in Eph receptors...
Excitatory Eph receptors and adhesive ephrin ligandsR Klein
European Molecular Biology Laboratory, Meyerhofstrasse 1, D 69117 Heidelberg, Germany
Curr Opin Cell Biol 13:196-203. 2001..The mode of action of ephrin/Ephs has been expanded from repulsion to adhesion and from cell surface attachment to regulated cleavage...
Membrane-bound LERK2 ligand can signal through three different Eph-related receptor tyrosine kinasesR Brambilla
European Molecular Biology Laboratory, Differentiation Programme, Heidelberg, Germany
EMBO J 14:3116-26. 1995..Quantitative analysis including binding assays indicates that Cek10 is the preferred LERK2 receptor. Preliminary mutagenesis of the LERK2 protein suggests a negative regulatory role for its cytoplasmic domain in LERK2 signaling...
The cytoplasmic domain of the ligand ephrinB2 is required for vascular morphogenesis but not cranial neural crest migrationR H Adams
European Molecular Biology Laboratory, Meyerhofstrasse 1, D 69117 Heidelberg, Germany
Cell 104:57-69. 2001..Our results indicate distinct requirements of functions mediated by the ephrinB carboxyterminus for developmental processes in the vertebrate embryo...
Coupling Met to specific pathways results in distinct developmental outcomesF Maina
European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117, Heidelberg, Germany
Mol Cell 7:1293-306. 2001..These data indicate that RTK-mediated activation of specific signaling pathways is required to fulfill cell-specific functions in vivo...
Kinase-dependent and kinase-independent functions of EphA4 receptors in major axon tract formation in vivoK Kullander
European Molecular Biology Laboratory, Meyerhofstrasse 1, D 69117, Heidelberg, Germany
Neuron 29:73-84. 2001..Unexpectedly, the cytoplasmic sterile-alpha motif (SAM) domain is not required for EphA4 functions. Our findings establish both kinase-dependent and kinase-independent functions of EphA4 in the formation of major axon tracts...
Point mutation in trkB causes loss of NT4-dependent neurons without major effects on diverse BDNF responsesL Minichiello
European Molecular Biology Laboratory, Heidelberg, Germany
Neuron 21:335-45. 1998....
The N-terminal globular domain of Eph receptors is sufficient for ligand binding and receptor signalingJ P Labrador
European Molecular Biology Laboratory, Heidelberg, Germany
EMBO J 16:3889-97. 1997..Our studies have determined the first structural elements involved in ligand-receptor interaction and will allow more fine-tuned genetic experiments to elucidate the mechanism of action of these important guidance molecules...
Roles of ephrinB ligands and EphB receptors in cardiovascular development: demarcation of arterial/venous domains, vascular morphogenesis, and sprouting angiogenesisR H Adams
European Molecular Biology Laboratory, D 69117 Heidelberg, Germany
Genes Dev 13:295-306. 1999....
Ephrin-B3 is the midline barrier that prevents corticospinal tract axons from recrossing, allowing for unilateral motor controlK Kullander
European Molecular Biology Laboratory, D 69117 Heidelberg, Germany
Genes Dev 15:877-88. 2001....
Multiple roles for hepatocyte growth factor in sympathetic neuron developmentF Maina
European Molecular Biology Laboratory, Heidelberg, Federal Republic of Germany
Neuron 20:835-46. 1998..Because Met and HGF are expressed in sympathetic ganglia throughout development, it is possible that the multiple effects of HGF/Met signaling on sympathetic neuroblasts and neurons occur in part by an autocrine mechanism...
Met receptor signaling is required for sensory nerve development and HGF promotes axonal growth and survival of sensory neuronsF Maina
Cell Regulation Programme, European Molecular Biology Laboratory, 69117 Heidelberg, Germany
Genes Dev 11:3341-50. 1997..In contrast, the actions of HGF on sensory neurons are mediated by Met effectors distinct from Grb2. Our findings demonstrate a requirement for Met signaling in neurons during development...
Signaling by Eph receptors and their ephrin ligandsK Brückner
European Molecular Biology Laboratory, Heidelberg, Germany
Curr Opin Neurobiol 8:375-82. 1998....
EphrinB ligands recruit GRIP family PDZ adaptor proteins into raft membrane microdomainsK Brückner
Developmental Biology Programme, European Molecular Biology Laboratory, Heidelberg, Germany
Neuron 22:511-24. 1999..Our findings suggest that GRIP proteins provide a scaffold for the assembly of a multiprotein signaling complex downstream of ephrinB ligands...
Essential role for TrkB receptors in hippocampus-mediated learningL Minichiello
European Molecular Biology Laboratory, Heidelberg, Germany
Neuron 24:401-14. 1999..Interestingly, heterozygotes show a partial but substantial reduction of LTP but appear behaviorally normal. Thus, CA1 LTP may need to be reduced below a certain threshold before behavioral defects become apparent...
Essential role of p38alpha MAP kinase in placental but not embryonic cardiovascular developmentR H Adams
European Molecular Biology Laboratory, Heidelberg, Germany
Mol Cell 6:109-16. 2000..Our results indicate that p38alpha is required for placental organogenesis but is not essential for other aspects of mammalian embryonic development...
The Eph receptor family: axonal guidance by contact repulsionD Orioli
Cell Regulation Programme, European Molecular Biology Laboratory, Heidelberg, Germany
Trends Genet 13:354-9. 1997..Here, we summarize the known biological functions of Eph receptors and ligands focusing on the developing nervous system, and we review the data on possible mechanisms of action...
Sek4 and Nuk receptors cooperate in guidance of commissural axons and in palate formationD Orioli
European Molecular Biology Laboratory, Heidelberg, Germany
EMBO J 15:6035-49. 1996..These results demonstrate essential and cooperative functions for Sek4 and Nuk in establishing axon pathways in the developing brain, and during the development of facial structures...
Similarities and differences in the way transmembrane-type ligands interact with the Elk subclass of Eph receptorsR Brambilla
European Molecular Biology Laboratory, Heidelberg, Germany
Mol Cell Neurosci 8:199-209. 1996..Knowledge regarding functional ligand-receptor interactions as presented in this study will be important for the design and interpretation of in vivo experiments, e.g., loss-of-function studies in transgenic mice...
The collagen receptor DDR2 regulates proliferation and its elimination leads to dwarfismJ P Labrador
European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany
EMBO Rep 2:446-52. 2001..Together our results suggest that DDR2 acts as an extracellular matrix sensor to modulate cell proliferation...
Hepatocyte growth factor, a versatile signal for developing neuronsF Maina
European Molecular Biology Laboratory, Heidelberg, Germany
Nat Neurosci 2:213-7. 1999..The broad spectrum of HGF activities and its observed synergy with other neurotrophic factors suggest that the major role of HGF is to potentiate the response of developing neurons to specific signals...
A role for the Ras signalling pathway in synaptic transmission and long-term memoryR Brambilla
European Molecular Biology Laboratory, Heidelberg, Germany
Nature 390:281-6. 1997..These results implicate Ras-GRF signalling via the Ras/MAP kinase pathway in synaptic events leading to formation of long-term memories...
TrkB and TrkC neurotrophin receptors cooperate in promoting survival of hippocampal and cerebellar granule neuronsL Minichiello
European Molecular Biology Laboratory, Heidelberg, Germany
Genes Dev 10:2849-58. 1996..Moreover, they suggest that central, in contrast to peripheral, neurons are capable of using more than one neurotrophin/Trk receptor signaling pathway to stay alive...
Uncoupling of Grb2 from the Met receptor in vivo reveals complex roles in muscle developmentF Maina
European Molecular Biology Laboratory, Heidelberg, Federal Republic of Germany
Cell 87:531-42. 1996..These data show that the requirements for Met signaling vary depending on the tissue and reveal a novel role for HGF/ Met in late myogenesis...
Nuk controls pathfinding of commissural axons in the mammalian central nervous systemM Henkemeyer
Programme in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
Cell 86:35-46. 1996..These results indicate that Nuk, a receptor that binds transmembrane ligands, plays a critical and unique role in the pathfinding of specific axons in the mammalian central nervous system...
Kinase-independent requirement of EphB2 receptors in hippocampal synaptic plasticityI C Grunwald
Department of Molecular Neurobiology, Max Planck Institute of Neurobiology, Am Klopferspitz 18a, D 82152, Martinsried, Germany
Neuron 32:1027-40. 2001..Interestingly, targeted expression of a carboxy-terminally truncated form of EphB2 rescued the EphB2 null phenotype, indicating that EphB2 kinase signaling is not required for these EphB2-mediated functions...
TrkB and neurotrophin-4 are important for development and maintenance of sympathetic preganglionic neurons innervating the adrenal medullaA Schober
Department of Anatomy and Cell Biology III, University of Heidelberg, D 69120 Heidelberg, Germany
J Neurosci 18:7272-84. 1998..These data are consistent with the notion that NT-4 from chromaffin cells operates through TrkB receptors to regulate development and maintenance of the preganglionic innervation of the adrenal medulla...
Developing inner ear sensory neurons require TrkB and TrkC receptors for innervation of their peripheral targetsT Schimmang
Departamento Bioquimica, Biologia Molecular y Fisiologia, Facultad de Medicina, Universidad de Valladolid, CSIC, Spain
Development 121:3381-91. 1995..TrkB and TrkC receptors are therefore required for the survival of specific neuronal populations and the maintenance of target innervation in the peripheral sensory system of the inner ear...
Beta1-class integrins regulate the development of laminae and folia in the cerebral and cerebellar cortexD Graus-Porta
Friedrich Miescher Institute, Maulbeerstr 66, 4058, Basel, Switzerland
Neuron 31:367-79. 2001..The phenotype of the beta1-deficient mice resembles pathological changes observed in human cortical dysplasias, suggesting that defective integrin-mediated signal transduction contributes to the development of some of these diseases...
Severe sensory and sympathetic neuropathies in mice carrying a disrupted Trk/NGF receptor geneR J Smeyne
Department of Molecular Biology, Bristol Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543 4000
Nature 368:246-9. 1994..These findings demonstrate that Trk is the primary mediator of the trophic actions of NGF in vivo and that this signalling pathway plays a crucial role in the development of both the peripheral and the central nervous systems...
ELF-2, a new member of the Eph ligand family, is segmentally expressed in mouse embryos in the region of the hindbrain and newly forming somitesA D Bergemann
Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
Mol Cell Biol 15:4921-9. 1995..Comparable patterns have been described for Eph family receptors, including Sek-4 and Nuk/Sek-3, suggesting roles for ELF-2 in patterning these regions of the embryo...
Similarities and differences in the way neurotrophins interact with the Trk receptors in neuronal and nonneuronal cellsN Y Ip
Regeneron Pharmaceuticals, Inc, Tarrytown, New York 10591
Neuron 10:137-49. 1993..However, we find that a neuronal environment does restrict the Trks in their ability to respond to their "nonpreferred" neurotrophin ligands...
Neutral endopeptidase terminates substance P-induced inflammation in allergic contact dermatitisT E Scholzen
Ludwig Boltzmann Institute for Cell Biology and Immunobiology of the Skin, Department of Dermatology, University of Munster, Munster, Germany
J Immunol 166:1285-91. 2001..Thus, these results indicate that NEP and cutaneous neuropeptides have a significant role in the pathogenesis of ACD...
Role of brain insulin receptor in control of body weight and reproductionJ C Bruning
Klinik II und Poliklinik für Innere Medizin and Center of Molecular Medicine ZMMK der Universität zu Köln, Joseph Stelzmann Strasse 9, 50931 Cologne, Germany
Science 289:2122-5. 2000..Thus, IR signaling in the CNS plays an important role in regulation of energy disposal, fuel metabolism, and reproduction...
Disruption of the neurotrophin-3 receptor gene trkC eliminates la muscle afferents and results in abnormal movementsR Klein
Department of Molecular Biology, Bristol Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543
Nature 368:249-51. 1994..These mice display abnormal movements and postures, indicating that NT3/TrkC-dependent sensor; neurons may play a primary role in proprioception, the sense of position and movement of the limbs...
Reduced acetylcholinesterase (AChE) activity in adrenal medulla and loss of sympathetic preganglionic neurons in TrkA-deficient, but not TrkB-deficient, miceA Schober
Department of Anatomy and Cell Biology III, University of Heidelberg, Germany
J Neurosci 17:891-903. 1997..Our results suggest that signaling via TrkA, but not TrkB, may be involved in the postnatal regulation of AChE activity in the adrenal medulla and its preganglionic nerves...
Ephrin-B3, a ligand for the receptor EphB3, expressed at the midline of the developing neural tubeA D Bergemann
Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
Oncogene 16:471-80. 1998..The isolation of this ligand may help to elucidate the molecular basis of patterning activities at the neural tube midline...
Timing of neuronal death in trkA, trkB and trkC mutant embryos reveals developmental changes in sensory neuron dependence on Trk signallingL G Pinon
School of Biological and Medical Sciences, University of St Andrews, Fife, Scotland, UK
Development 122:3255-61. 1996..These results demonstrate that TrkB signalling is required for the in vivo survival of many trigeminal neurons during the early stages of target field innervation before they become NGF-dependent...
Aberrant neural and cardiac development in mice lacking the ErbB4 neuregulin receptorM Gassmann
Molecular Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037, USA
Nature 378:390-4. 1995....
Tyro-3 family receptors are essential regulators of mammalian spermatogenesisQ Lu
Molecular Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037, USA
Nature 398:723-8. 1999..Additional observations indicate that these receptors may also be essential for the tropic maintenance of diverse cell types in the mature nervous, immune and reproductive systems...
Differential effects of combined trk receptor mutations on dorsal root ganglion and inner ear sensory neuronsL Minichiello
Differentiation Programme, European Molecular Biology Laboratory, Heidelberg, Germany
Development 121:4067-75. 1995..This effect was not observed in DRGs, where neurons depending on different Trk receptors generally innervate different targets...
Targeted disruption of the trkB neurotrophin receptor gene results in nervous system lesions and neonatal deathR Klein
Department of Molecular Biology, Bristol Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543 4000
Cell 75:113-22. 1993..These findings illustrate the role of the gp145trkB protein-tyrosine kinase receptor in the ontogeny of the mammalian nervous system...
The branchial arches and HGF are growth-promoting and chemoattractant for cranial motor axonsA Caton
Centre for Developmental Neurobiology, King s College, Guy s Campus, London SE1 9RT, UK
Development 127:1751-66. 2000..This influence is likely to be mediated partly by Hepatocyte Growth Factor, although a component of branchial arch-mediated growth promotion and chemoattraction was not blocked by anti-HGF antibodies...
Survival of inner ear sensory neurons in trk mutant miceT Schimmang
Instituto de Biologia y Genetica Molecular, Universidad de Valladolid y Consejo Superior de Investigaciones Cientificas, Facultad de Medicina, Spain
Mech Dev 64:77-85. 1997....
