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| [[Image:CoverLeBorgne.jpg]] | | [[image:Cover_web_page_OpenWetWarebis.tif]] |
| ==Contact Info== | | <div style="padding: 20px; color: #ffffff; background-color: #000; width: 1045px"> |
| [[Image:LeBorgne1.jpg|thumb|]]
| | <center> |
| *'''Roland Le Borgne'''
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| *CNRS UMR 6061
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| *[http://www.umr6061.univ-rennes1.fr/ Institut de Génétique et Développement-IGDR]
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| *[http://www.umr6061.univ-rennes1.fr/equipes/recherche_equipe.php?domaine=&equipe=35&resp_equipe= Team]
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| *Faculté de Médecine
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| *2 avenue du Pr Bernard
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| *35000 Rennes
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| *France
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| *''roland.leborgne@univ-rennes1.fr''
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| *phone: 33 223234894/0686058923
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| ==Education and awards== | | [[LeBorgne| <font face="Helvetica" style="color:#ffffff"> '''Home''' </font>]] |
| <!--Include info about your educational background--> | | [[LeBorgne:Contact | <font face="Helvetica" style="color:#faf342"> '''Contact''' </font>]] |
| * 1995, PhD, EMBL-Heidelberg Germany
| | [[LeBorgne:Back Door | <font face="Helvetica" style="color:#faf342"> '''Position/news''' </font>]] |
| * 1996-1999, post doctoral training at the Institut de Biology de Lille, France
| | [[LeBorgne:Lab Members | <font face="Helvetica" style="color:#faf342"> '''Lab Members''' </font>]] |
| * 1999-2005, CNRS researcher at the ENS (Ecole Normale Supérieure), Paris, France
| | [[LeBorgne:Publications | <font face="Helvetica" style="color:#faf342"> '''Publications''' </font>]] |
| * 2003 bronze medal from the CNRS
| | [[LeBorgne:Research | <font face="Helvetica" style="color:#faf342"> '''Research''' </font>]] |
| * 2006 HDR, University de Rennes
| | [[LeBorgne:Collaborators | <font face="Helvetica" style="color:#faf342"> '''Collaborators''' </font>]] |
| * 2006-present ATIP Programme CNRS, Institut de Génétique et Développement de Rennes, France
| | [[LeBorgne:Talks | <font face="Helvetica" style="color:#faf342"> '''Useful links''' </font>]] |
| | </center> |
| | </div><br> |
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| ==Research interests==
| | The team was created in 2006 thanks to the CNRS ATIP programme 'Developmental Cell Biology' |
| <!-- Feel free to add brief descriptions to your research interests as well -->
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| [[Image:Numb-1.jpg|thumb|Unequal segregation of Numb (red) in dividing SOP, tubulin (green)]]
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| # Asymmetric cell division is a conserved mechanism by which cell fate diversity is generated during Metazoan development. How one cell can generate two daughter cells with different identities and how defects in this asymmetry can contribute to cancer are the fundamental questions we are addressing in Drosophila. We are investigating this process in the context of asymmetric cell division of neural precursor cells, called Sensory Organ Precursor (SOP). These latter undergo four rounds of asymmetric divisions, in which mother cells generate distinct daughters via the unequal segregation of the cell-fate determinants Numb and Neuralized at mitosis. At each division binary cell fate decision are regulated by Delta-Notch dependent cell-cell signalling. Numb is an endocytic protein that can bind to Notch and a four pass transmembrane protein named Sanpodo (Spdo), a protein required for Notch activation in SOP lineage, thereby preventing Notch activation in this cell. Neur acts in SOPs and pIIb cells to regulate the endocytosis and signalling activity of Dl, thereby promoting N activation in non-SOP (lateral inhibition) and pIIa cells (binary cell fate decision), respectively. Despite intensive studies, the mechanism whereby Neur regulates Dl activity is not known. Two non-exclusive models have been proposed to explain the role of ubiquitin-dependent endocytosis of Dl in Notch receptor activation. First, the ‘pulling’ model proposes that internalization of Dl bound to its receptor exerts pulling forces on Notch and induces a conformational change exposing the S2 cleavage site to metalloproteases. Alternatively, the ‘activation/recycling’ model proposes that internalization is required to promote the formation of active ligands that are recycled back to the cell surface to activate Notch1. However the nature of the ligand activation and the subcellular localisation where recycled Dl could interact with Notch to produce signalling remained unknown. Our research aims to understand how intracellular trafficking contributes to the definition of the polarity axis of the divisions and ensure the proper spatio-temporal regulation of Notch-dependent fate decision.
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| ==People==
| | and is hosted within the Institute of Genetic and Development (Rennes, France): *[http://igdr.univ-rennes1.fr/ Institut de Génétique et Développement de Rennes] |
| '''Permanent positions'''
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| [[Image:Group Le Borgne.jpg|thumb|Lab Members early 2010]]
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| *Roland Le Borgne, PI, DR2 CNRS
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| *Solange Monier, CR1 INSERM
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| *Stéphanie Le Bras, MCU, université deRennes 1
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| '''Postdoctoral Fellows'''
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| *Christine Rondanino, INCA
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| *Mathieu Cotton, UR1
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| '''Graduate Students'''
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| *Nabila Founounou, Ared Région Bretagne
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| *Nicolas Loyer, MNERT
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| '''Technical Ingeneers and Research Technicians'''
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| *Vignaux Françoise, I.E.1 CNRS
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| '''Past members'''
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| *Najate Benhra, Post-doctoral fellow in M. Milan's lab, IRB Barcelona (http://www.irbbarcelona.org/mmilan) | |
| *Sylvie Lallet Scientific Project manager at GNM healthcare consulting Group
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| *Aurore Dussert =>Marek Mlodzik's Lab (in September 2010)
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| == Scientific collaborations ==
| | Main interests: |
| *Role of exovesicles in Wnt gradient formation [http://www.nimr.mrc.ac.uk/research/jean-paul-vincent Jean-Paul Vincent]
| | [[Image:Numb-1.jpg|thumb|Unequal segregation of Numb (red) in dividing SOP, tubulin (green)]] |
| *Function of clathrin adaptor AP-1 complex in mucin type granules biogenesis [http://www.sickkids.ca/AboutSickKids/Directory/People/B/Julie-Brill-Staff-Profile.html Julie Brill]
| | Asymmetric cell division is a conserved mechanism by which cell fate diversity is generated during Metazoan development. How one cell can generate two daughter cells with different identities and how defects in this asymmetry can contribute to cancer are the fundamental questions we are addressing in Drosophila. We are investigating this process in the context of asymmetric cell division of neural precursor cells, called Sensory Organ Precursor (SOP). These latter undergo four rounds of asymmetric divisions, in which mother cells generate distinct daughters via the unequal segregation of the cell-fate determinants Numb and Neuralized at mitosis. At each division binary cell fate decision are regulated by Delta-Notch dependent cell-cell signalling. Numb is an endocytic protein that can bind to Notch and a four pass transmembrane protein named Sanpodo (Spdo), a protein required for Notch activation in SOP lineage, thereby preventing Notch activation in this cell. Neur acts in SOPs and pIIb cells to regulate the endocytosis and signalling activity of Dl, thereby promoting N activation in non-SOP (lateral inhibition) and pIIa cells (binary cell fate decision), respectively. Despite intensive studies, the mechanism whereby Neur regulates Dl activity is not known. Two non-exclusive models have been proposed to explain the role of ubiquitin-dependent endocytosis of Dl in Notch receptor activation. First, the ‘pulling’ model proposes that internalization of Dl bound to its receptor exerts pulling forces on Notch and induces a conformational change exposing the S2 cleavage site to metalloproteases. Alternatively, the ‘activation/recycling’ model proposes that internalization is required to promote the formation of active ligands that are recycled back to the cell surface to activate Notch1. However the nature of the ligand activation and the subcellular localisation where recycled Dl could interact with Notch to produce signalling remained unknown. Our research aims to understand how intracellular trafficking contributes to the definition of the polarity axis of the divisions and ensure the proper spatio-temporal regulation of Notch-dependent fate decision. |
| *Role of Neuralized in Delta trafficking [http://francois.schweisguth.free.fr/ François Schweisguth]
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| ==Selected publications==
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| <!-- Replace the PubMed ID's ("pmid=#######") below with the PubMed ID's for your publications. You can add or remove lines as needed -->
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| # Benhra N., Lallet L. , Cotton M., Le Bras S., Dussert A. and '''Le Borgne R.''' (2011) AP-1 controls the trafficking of Notch and Sanpodo
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| towards the E-Cadherin junctions in sensory organ precursors, Current Biology 21, 87-95
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| # Benhra N., Vignaux F., Dussert A., Schweisguth F. and '''Le Borgne R.''' (2010) Neuralized promotes basal to apical transcytosis of Delta in epithelial cells Molecular Biology of the Cell 21, 2078-86 (Cover Picture)
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| # Dif A, Boulmedais F, Pinot M, Roullier V, Baudy-Floc'h M, Coquelle FM, Clarke S, Neveu P, Vignaux F, '''Le Borgne R''', Dahan M, Gueroui Z, Marchi-Artzner V (2009) Small and stable peptidic PEGylated quantum dots to target polyhistidine-tagged proteins with controlled stoichiometry J. am. Chem. Soc. 131(41):14738-46.
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| # Smith CA, Lau KM, Rahmani Z, Dho SE, Brothers G, She YM, Berry DM, Bonneil E, Thibault P, Schweisguth F, '''Le Borgne R''', McGlade CJ. (2007) aPKC-mediated phosphorylation regulates asymmetric membrane localization of the cell fate determinant Numb. EMBO J. 2007 Jan 24;26(2):468-80
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| # Langevin,L., '''Le Borgne,R'''., (equal contribution), Rosenfeld, F., Gho,M., Schweisguth, F. and Bellaïche, Y. (2005). Lethal giant larvae controls the localisation of the Notch signalling regulators Numb, Neuralized and Sanpodo in Drosophila sensory organ precursor cells. Current Biology 15, 955-62
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| #'''Le Borgne R.''', Remaud, S., Hamel,S., and Schweisguth F (2005). The E3 ubiquitin ligases Mind bomb and Neuralized have distinct and complementary functions in the regulation of Delta and Serrate activity in drosophila. PLoS Biology 3, e96
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| #''''Le Borgne R.''' and Schweisguth, F. (2003). Unequal segregation of Neuralized biases Notch activation during asymmetric cell division. Developmental Cell 5(1), 139-148
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| [[Image:F1000biology.gif]]
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| # '''Le Borgne R.''', Bellaïche Y.and Schweisguth F.(2002) Drosophila E-Cadherin regulates the orientation of asymetric cell division in the sensory organ lineage, Current Biology, 12, 95-104
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| # Ben-Yaacov, S., '''Le Borgne, R.''', Abramson, I., Schweisguth,F. , and Schejter, E. D. (2001). Wasp, The Drosophila Wiskott-Aldrich Syndrome Gene Homolog, Is Required For Cell Fate Decisions Mediated By Notch Signaling . J. Cell Biol. 152, 1-13
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| #10 Waguri S., Dewitte F., '''Le Borgne R.''', Rouille Y., Uchiyama Y., Dubremetz JF, and Hoflack B. (2003). Visualization of TGN to Endosome Trafficking through Fluorescently Labeled MPR and AP-1 in Living Cells. Mol Biol Cell. 14(1):142-55
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| # '''Le Borgne R.''' and Hoflack B. (1998). Mechanisms of protein sorting and coat assembly: insights from the clathrin-coated vesicle pathway. Curr. Opin. Cell Biol. 10: 499-503
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| # '''Le Borgne R.''', Alconada A., Bauer U., and Hoflack B. (1998). The mammalian AP-3 adaptor-like complex mediates the intracellular transport of lysosomal membrane glycoproteins. J. Biol. Chem. 273: 29451-29461
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| # '''Le Borgne R.''', and Hoflack B. (1997). The mannose 6-phosphate receptors regulate the formation of clathrin-coated vesicles in the trans-Golgi network. J. Cell Biol. 137: 335-345
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| # '''Le Borgne R.''', Griffiths G., and Hoflack B. (1996). Mannose 6-phosphate receptors and ADP-ribosylation factors cooperate for high affinity interaction of the AP-1 Golgi-assembly proteins with membranes. J. Biol. Chem. 271: 2162-2170
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| # '''Le Borgne R.''', Schmidt A., Mauxion F., Griffiths G., and Hoflack B. (1993). Binding of AP-1 Golgi adaptors to membranes requires phosphorylated cytoplasmic domains of the mannose 6-phosphate/insulin-like growth factor II receptor. J. Biol. Chem. 268: 22552-22556
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| ==Reviews and Comments==
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| <!-- Replace the PubMed ID's ("pmid=#######") below with the PubMed ID's for your publications. You can add or remove lines as needed -->
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| # Le Bras,S., Loyer, N. and '''Le Borgne,R.''' (2011). The multiple facets of ubiquitination in the regulation of Notch signaling pathway. Traffic 12(2):149-61
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| # '''Le Borgne,R.''' (2006). Regulation of Notch signalling by endocytosis and endosomal sorting. Curr Opin Cell Biol. 18(2), 213-22
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| # '''Le Borgne, R'''., Bardin, A. and Schweisguth F. (2005) Roles of receptor and ligand endocytosis in the regulation of Notch signaling. Development 132, 1751-62
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| # Bardin, A.J., '''Le Borgne, R'''., Schweisguth F. (2004). Asymmetric localization and function of cell-fate determinants: a fly's view. Curr Opin Neurobiol. Feb;14(1):6-14
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| # '''Le Borgne, R.''' and Schweisguth, F. (2003). Notch signaling: endocytosis makes Delta signal better. Curr. Biol. 23, R273-R275
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| # '''Le Borgne, R.''', and Hoflack, B. (1998). Protein transport from the secretory to the endocytic pathway in mammalian cells. Bioch. Biophys. Acta: thematic Issue on « The Golgi Complex », 1404: 195-209
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| # Ludwig,T., '''Le Borgne,R.''', and Hoflack,B. (1995). Roles for mannose 6-phosphate receptors in lysosomal emzyme sorting, IGF-II binding and clathrin-coat assembly. Trends in Cell Biol. 5: 202-206
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| ==Useful links==
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| *[http://www.umr6061.univ-rennes1.fr/ Institut de Génétique et Développement de Rennes]
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| *[http://f1000.com/search/evaluations?query=Le+Borgne-r/ Le Borgne's publications evaluated in Faculty of 1000]
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| *[http://www.sfbd.fr/ Société Francaise de Biologie du Développement SFBD]
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| *[http://www.sbcf.fr/ Société de Biologie Cellulaire de France SBCF]
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| *[http://www.cnrs.fr/ CNRS]
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| *[http://flybase.org/ FlyBase]
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| *[http://smart.embl-heidelberg.de/smart/set_mode.cgi?NORMAL=1 SMART]
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| *[[OpenWetWare:Welcome|Introductory tutorial]]
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| *[[Help|OpenWetWare help pages]]
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