Papers by Dominique Bagnard
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience
The Unc-33-like phosphoprotein/collapsin response mediator protein (Ulip/CRMP) family consists of... more The Unc-33-like phosphoprotein/collapsin response mediator protein (Ulip/CRMP) family consists of four homologous phosphoproteins considered crucial for brain development. Autoantibodies produced against member(s) of this family by patients with paraneoplastic neurological diseases have made it possible to clone a fifth human Ulip/CRMP and characterize its cellular and anatomical distribution in developing brain. This protein, referred to as Ulip6/CRMP5, is highly expressed during rat brain development in postmitotic neural precursors and in the fasciculi of fibers, suggesting its involvement in neuronal migration/differentiation and axonal growth. In the adult, Ulip6/CRMP5 is still expressed in some neurons, namely in areas that retain neurogenesis and in oligodendrocytes in the midbrain, hindbrain, and spinal cord. Ulip2/CRMP2 and Ulip6/CRMP5 are coexpressed in postmitotic neural precursors at certain times during development and in oligodendrocytes in the adult. Because Ulip2/CRMP2 has been reported to mediate semaphorin-3A (Sema3A) signal in developing neurons, in studies to understand the function of Ulip6/CRMP5 and Ulip2/CRMP2 in the adult, purified adult rat brain oligodendrocytes were cultured in a Sema3A-conditioned medium. Oligodendrocytes were found to have Sema3A binding sites and to express neuropilin-1, the major Sema3A receptor component. In the presence of Sema3A, these oligodendrocytes displayed a dramatic reduction in process extension, which was reversed by removal of Sema3A and prevented by anti-neuropilin-1, anti-Ulip6/CRMP5, anti-Ulip2/CRMP2 antibodies, or VEGF-165, another neuropilin-1 ligand. These results indicate the existence in the adult brain of a Sema3A signaling pathway that modulates oligodendrocyte process extension mediated by neuropilin-1, Ulip6/CRMP5, and Ulip2/CRMP2, and they open new fields of investigation of neuron/oligodendrocyte interactions in the normal and pathological brain.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience
ABSTRACT
Revue Neurologique
During embryonic and post-natal development, numerous axonal connections are formed establishing ... more During embryonic and post-natal development, numerous axonal connections are formed establishing a functional nervous system. Knowledge of the underlying molecular and cellular mechanisms controlling this phenomenon is improving. In this review, we present the general principles of axon guidance together with the major families of guidance signals. This includes the tyrosine kinase receptors Eph and their ligands Ephrins, the netrins, the semaphorins, the slits and other major components of the extracellular matrix. These types of guidance signals share common functional properties leading to actin cytoskeleton remodelling. The direct or indirect interactions between the receptors of these guidance cues and actin modulators is the final step of the signalling cascade constituting the fundamental mechanism defining the orientation and extension of the axonal growth cone. These factors are involved in the formation of many, if not all, axonal projections for which they act as repulsive (inhibitory) or attractive (promoting) signals. the knowledge of these mechanisms is particularly interesting since the inhibition of axonal outgrowth is considered to be one of the major obstacles to nerve regeneration in the central nervous system. Indeed, most of the guidance signals expressed during brain development are up-regulated in lesion sites where they contribute to the lack of nerve re-growth. Here, we present the nature of the mechanical barrier, the so called glial scar, and we describe the major inhibitory molecules preventing axonal extension. the comprehension of the molecular mechanisms involved in axon growth and guidance represents a major advance towards the definition of novel therapeutic strategies improving nerve regeneration. The path to the clinical application of these molecular factors remains long. Nevertheless, the next decade will undoubtedly provide challenging data that will modify the current therapeutic approaches.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience
ABSTRACT
Neuropilin-1 (NRP1) is a transmembrane receptor playing a pivotal role in the control of semaphor... more Neuropilin-1 (NRP1) is a transmembrane receptor playing a pivotal role in the control of semaphorins and VEGF signaling pathways. The exact mechanism controlling semaphorin receptor complex formation is unknown. A structural analysis and modeling of NRP1 revealed a putative dimerization GxxxG motif potentially important for NRP1 dimerization and oligomerization. Our data show that this motif mediates the dimerization of the
Ciba Foundation symposium
The functioning of the adult mammalian cerebral cortex depends critically upon precise interconne... more The functioning of the adult mammalian cerebral cortex depends critically upon precise interconnections between specific thalamic nuclei and distinct cortical regions. Therefore, one central issue in understanding cortical development is determining the cellular and molecular strategies underlying the specification of thalamocortical projections. We address the role of axon-axon interactions and membrane-bound guidance molecules in the establishment of the development of layer-specific patterns of afferent and efferent cortical connections does not depend upon neuronal activity. We present evidence that activity conveyed by thalamic afferents is required for the elaboration of the columnar specificity of cortical circuits.
Advances in experimental medicine and biology, 2007
... and Guidance Eric Kondna, Lise Roth, Bertand Gonthier and Dominique Bagnard* Introduction Dur... more ... and Guidance Eric Kondna, Lise Roth, Bertand Gonthier and Dominique Bagnard* Introduction During development, neuronal growth cones navigate over long distances to reach their target and establish appropriate connections. ... 32. Bouzioukh F, Daoudal G, Falk J et al. ...
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2000
It is generally assumed that gradients of chemotropic molecules are instrumental to the wiring of... more It is generally assumed that gradients of chemotropic molecules are instrumental to the wiring of the nervous system. Recently, two members of the secreted class III semaphorin protein family have been implicated as repulsive (Sema3A) and attractive (Sema3C) guidance molecules for cortical axons (). Here, we show that stabilized gradients of increasing semaphorin concentrations elicit stereotyped responses from cortical growth cones, independent of the absolute concentration and the slope of these gradients. In contrast, neither repulsive effects of Sema3A nor attractive effects of Sema3C were observed when axons were growing toward decreasing semaphorin concentrations. Thus, growth cone guidance by gradients of chemotropic molecules is robust and reproducible, because it is primarily independent of the exact dimensions of the gradients.
Springer Protocols Handbooks, 2009
Culturing neurons is an effective way to analyze the basic mechanisms that govern nervous system ... more Culturing neurons is an effective way to analyze the basic mechanisms that govern nervous system wiring. The choice of an appropriate molecular substrate is of prime importance to the main objective of the culture. We describe the preparation of basic 2D substrates, complex 2D ...
Biovalley Monographs, 2005
The precise cytoarchitecture of the cerebral cortex ensures appropriate treatment of sensory and ... more The precise cytoarchitecture of the cerebral cortex ensures appropriate treatment of sensory and motor information. Hence, the cortex is the basis of perception, behavior and consciousness. The mature neocortex is composed of six distinct layers [1] characterized ...
International Journal of Developmental Neuroscience, 2006
Cell Reports, 2014
Breast cancer is still a deadly disease despite major achievements in targeted therapies designed... more Breast cancer is still a deadly disease despite major achievements in targeted therapies designed to block ligands or ligand-binding subunits of major tyrosine kinase receptors. Relapse is significant and metastases deleterious, which demands novel strategies for fighting this disease. Here, we report a proof-of-concept experiment demonstrating that small peptides interfering with the transmembrane domain of the tyrosine kinase epidermal growth factor receptor ErbB2 exhibit anticancer properties when used at micromolar dosages in a genetically engineered mouse model of breast cancer. Different assays demonstrate the specificity of the ErbB2-targeting peptide, which induces long-term reduction of ErbB2 phosphorylation and Akt signaling consistent with reduced tumor cell proliferation and increased survival. Microcomputed tomography analysis established the antimetastatic activity of the peptide and its impact on primary tumor growth. This reveals the interior of the cell membrane as an unexplored dimension for drug design.
Journal of Molecular Biology, 2014
Signaling in eukaryotic cells frequently relies on dynamic interactions of single-pass membrane r... more Signaling in eukaryotic cells frequently relies on dynamic interactions of single-pass membrane receptors involving their transmembrane (TM) domains. To search for new such interactions, we have developed a bacterial two-hybrid system to screen for both homotypic and heterotypic interactions between TM helices. We have explored the dimerization of TM domains from 16 proteins involved in both receptor tyrosine kinase and neuropilin signaling. This study has revealed several new interactions. We found that the TM domain of Mucin-4, a putative intramembrane ligand for erbB2, dimerizes not only with erbB2 but also with all four members of the erbB family. In the Neuropilin/Plexin family of receptors, we showed that the TM domains of Neuropilins 1 and 2 dimerize with themselves and also with Plexin-A1, Plexin-B1, and L1CAM, but we were unable to observe interactions with several other TM domains notably those of members of the VEGF receptor family. The potentially important Neuropilin 1/Plexin-A1 interaction was confirmed using a surface plasmon resonance assay. This work shows that TM domain interactions can be highly specific. Exploring further the propensities of TM helix-helix association in cell membrane should have important practical implications related to our understanding of the structure-function of bitopic proteins' assembly and subsequent function, especially in the regulation of signal transduction.
Trends in Cell Biology, 2002
Trends in Cell Biology, 2002
Trends in Cell Biology, 2002
Trends in Cell Biology, 2001
Bioconjugate chemistry, 2015
pH-sensitive linkers designed to undergo selective hydrolysis at acidic pH compared to physiologi... more pH-sensitive linkers designed to undergo selective hydrolysis at acidic pH compared to physiological pH can be used for selective release of therapeutics selectively at targets and orthoesters have demonstrated to be good candidate for such linkers. Following an HPLC screen, a Spiro Di-orthoester (SpiDo) derivative was identified as a potent acid-labile group for the development of pH-sensitive targeted systems. After incorporation of this linker into activatable FRET-based probe and side-by-side comparison to a well-known alkylhydrazone linker, this SpiDo linker has shown a fast and pH sensitive hydrolysis for mild acidic conditions, a pH sensitive lysosomal hydrolysis and a high stability in Human plasma.
Trends in Cell Biology, 2001
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Papers by Dominique Bagnard