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Accueil > Agenda > Les séminaires Jean Roche > Guidage de la migration des précurseurs du cervelet

Guidage de la migration des précurseurs du cervelet

Lundi 30 janvier 2006,11h, salle Lissitzky.

Bibliographie

1 : Int Immunol. 2005 Apr ;17(4):439-47. Epub 2005 Mar 3.

Soluble CD100 functions on human monocytes and immature dendritic cells require plexin C1 and plexin B1, respectively.

Chabbert-de Ponnat I, Marie-Cardine A< /a>, Pasterkamp RJ, Schiavon V, Tamagnone L, Thomasset N, Bensussan A, Boumsell L.

INSERM U448, Faculty of Medicine, 8 rue du General Sarrail, 94010 Creteil Cedex, France.

CD100 represents the first semaphorin described in the immune system. It is expressed as a 300-kDa homodimer at the surface of most hematopoietic cells, but is also found in a soluble form following a proteolytic cleavage upon cell activation. We herein established that soluble CD100 (sCD100) impaired the migration of human monocytes and immature dendritic cells (DCs), but not of mature DCs. Performing competition assays, we identified plexin C1 (VESPR/CD232) as being involved in sCD100-mediated effects on human monocytes. Interestingly, we observed a complete down-regulation of plexin C1 expression during the in vitro differentiation process of monocytes to immature DCs, while concomitantly the surface expression of plexin B1 was induced. The latter receptor then binds sCD100 on immature DCs, mediating its inhibitory effect on cell migration. Finally, we showed that sCD100 modulated the cytokine production from monocytes and immature DCs. Together these results suggest that sCD100 plays a critical role in the regulation of antigen-presenting cell migration and functions via a tightly regulated process of receptor expression.

2 : Mol Cell Neurosci. 2004 Apr ;25(4):722-31.

Differential MAP kinases activation during semaphorin3A-induced repulsion or apoptosis of neural progenitor cells.

Bagnard D, Sainturet N, Meyronet D, Perraut M, Miehe M, Roussel G, Aunis D, Belin MF, Thomasset N.

INSERM U575, "Physiopathologie du Systeme Nerveux", 67084 Strasbourg, France. bagnard neurochem-u-strasbg.fr

Semaphorins are multifunctional factors implicated in various developmental processes. Little is known about the intracellular pathways ensuring appropriate signal transduction that encode the diverse functions observed. In this study, we investigated whether mitogen-activated protein kinases (MAPK), which are key elements of signal transduction in eukaryotic cells, were activated during semaphorin 3A (Sema3A)-induced repulsion or apoptosis of neural progenitor cells. We found that selective recruitment of the ERK1/2 pathway occurred during Sema3A-induced neural progenitor cell repulsion, whereas p38 MAPK activation was necessary for induction of apoptosis. Moreover, we provide evidence for the involvement of vascular endothelial growth factor receptor 1 (VEGFR1) in the activation of ERK1/2. Additional experiments performed with native cerebellar progenitors confirmed such a selective recruitment of MAPK during Sema3A-dependent migration or apoptosis. Altogether, our results suggest a model to explain how a single factor can exert different functions for a given cell type by the selective recruitment of intracellular pathways.

http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6WNB-4BS0F27-4-D&_cdi=6958&_user=113324&_orig=search&_coverDate=04%2F30%2F2004&_qd=1&_sk=999749995&view=c&wchp=dGLbVzz-zSkWW&md5=19969e76361b6cbbbda3d7bf7903c7f3&ie=/sdarticle.pdf

3 : Mol Cell Neurosci. 2003 Oct ;24(2):395-408.

MMP-9 deficiency affects axonal outgrowth, migration, and apoptosis in the developing cerebellum.

Vaillant C, Meissirel C, Mutin M, Belin MF, Lund LR, Thomasset N.

Institut National de la Sante et de la Recherche Medicale U433, Neurobiologie Experimentale et Physiopathologie, Faculte de Medecine Laennec, 69372 Lyon cedex 08, France.

Matrix metalloproteinases (MMPs) are responsible for the extens ive extracellular proteolysis that plays a central role in regulating the pericellular environment, contributing to morphogenesis and developmental remodeling. In the CNS, there is increasing in vitro evidence for the involvement of MMPs in neurite elongation and axonal guidance. Here, we show that expression of MMP-9 is spatiotemporally related to cerebellar granule cell migration during postnatal development. Using cerebellar explant cultures, we demonstrated that a specific MMP-9-blocking antibody affects granular cell axonal outgrowth and migration in a dose-dependent manner. In addition, the in vivo analysis of MMP-9-deficient mice revealed abnormal accumulation of granular precursors (GPs) in the external granular layer (EGL) at a time when migration is normally extensive. Furthermore, GP migration was delayed and their programmed cell death was reduced in MMP-9-deficient mice, suggesting that MMP-9 is involved in the control of granule cell migration and apoptosis. These results provide direct evidence for a physiological role of MMP-9 in neuronal precursor migration and apoptosis in the developing cerebellum, and emphasize the importance of MMP-9 in the temporal regulation of the cerebellar microenvironment.

http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6WNB-496NKDJ-4-K&_cdi=6958&_user=113324&_orig=search&_coverDate=10%2F31%2F2003&_qd=1&_sk=999759997&view=c&wchp=dGLbVtz-zSkWb&md5=aad4a9298b924db76f983982b4fbc941&ie=/sdarticle.pdf

4 : Mol Neurobiol. 2003 Aug ;28(1):51-64.

Collapsin response mediator proteins (CRMPs) : involvement in nervous system development and adult neurodegenerative disorders.

Charrier E, Reibel S, Rogemond V, Aguera M, Thomasset N, Honnorat J.

Institut National de la Sante et de la Recherche Medicale U 433, Hopital Neurologique, 59 Bd Pinel, 69003 Lyon, France.

The members of the collapsin response mediator protein (CRMP) family-five c ytosolic phosphoproteins -are highly expressed throughout brain development. The first member to be cloned, CRMP2, was identified as an intracellular messenger required for the growth cone-collapse induced by semaphorin 3A (Sema3A). A rapidly expanding body of study indicates that the functions of CRMPs are not solely limited to the signaling transduction of the Sema3A guidance cue. They are probably involved in multiple cellular and molecular events involved in apoptosis/proliferation, cell migration, and differentiation. In the adult brain, the expression of CRMPs is dramatically downregulated. However, they remain expressed in structures that retain their capacity for differentiation and plasticity and also in a subpopulation of oligodendrocytes (CRMP2 and CRMP5). Moreover, the expression of CRMPs is altered in neurodegenerative diseases, and these proteins may be of key importance in the physiopathology of the adult nervous system.

Publication Types : · Review

5 : J Neurosci. 2001 Sep 15 ;21(18):7203-14.Related Articles, Compound via MeSH, Substance via MeSH, Cited in PMC, Books, LinkOut

Isolation and expression pattern of human Unc-33-like phosphoprotein 6/collapsin response mediator protein 5 (Ulip6/CRMP5) : coexistence with Ulip2/CRMP2 in Sema3a- sensitive oligodendrocytes.

Ricard D, Rogemond V, Charrier E, Aguera M, Bagnard D, Belin MF, Thomasset N, Honnorat J.

Institut National de la Sante et de la Recherche Medicale U 433, Institut Federatif des Neurosciences de Lyon, Hopital Neurologique, 69003 Lyon, France.

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.

http://www.jneurosci.org/cgi/reprint/21/18/7203.pdf

6 : J Neurosci. 2001 May 15 ;21(10):3332-41.

Semaphorin 3A-vascular endothelial growth factor-165 balance mediates migration and apoptosis of neural progenitor cells by the recruitment of shared receptor.

Bagnard D, Vaillant C, Khuth ST, Dufay N, Lohrum M, Puschel AW, Belin MF, Bolz J, Thomasset N.

Institut National de la Sante et de la Recherche Medicale U433, Neurobiologie Experimentale et Physiopathologie, Faculte de Medecine Laennec, 69372 Lyon cedex 08, France.

The dynamic and coordinated interaction between cells and their microenvironment controls cell migration, proliferation, and apoptosis, mediated by different cell surface molecules. We have studied the response of a neuroectodermal progenitor cell line, Dev, to a guidance molecule, semaphorin 3A (Sema3A), described previously as a repellent-collapsing signal for axons, and we have shown that Sema3A acts as a repellent guidance cue for migrating progenitor cells and, on prolonged application, induces apoptosis. Both repulsion and induction of cell death are mediated by neuropilin-1, the ligand-binding component of the Sema3A receptor. The vascular endothelial growth factor, VEGF165, antagonizes Sema3A-induced apoptosis and promotes cell survival, migration, and proliferation. Surprisingly, repulsion by Sema3A also depends on expression of VEGFR1, a VEGF165 receptor, expressed in Dev cells. Moreover, we found that these repulsive effects of Sema3A require tyrosine kinase activity, which can be attributed to VEGFR1. These results indicate that the balance between guidance molecules and angiogenic factors can modulate the migration, apoptosis (or survival), and proliferation of neural progenitor cells through shared receptors.

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