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<!-- Feel free to add brief descriptions to your research interests as well -->
<!-- Feel free to add brief descriptions to your research interests as well -->
[[Image:Numb-1.jpg‎‎|thumb|Unequal segregation of Numb (red) in dividing SOP, tubulin (green)]]
[[Image:Numb-1.jpg‎‎|thumb|Unequal segregation of Numb (red) in dividing SOP, tubulin (green)]]
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.
Asymmetric cell division (ACD) is a conserved mechanism by which cell fate diversity is generated during development and throughout adult life. How a cell can produce two daughter cells with different identities and how defects in this asymmetry contribute to diseases are the fundamental questions we study using the Drosophila adult sensory organ (SO) lineage as a model system. SO Precursors (SOP) are epithelial cells present in a single layer neuroepithelium on the dorsal thorax of Drosophila. SOP undergoes a series of four ACD in which a mother cell gives rise to two daughter cells via uneven segregation of the Notch regulators Numb and Neuralized. Thus, at each division, the acquisition of cell identity is controlled by the differential activation of Notch. Notch is activated by Delta (Dl) present on the surface of adjacent cells. Our recent work contributed to show that sorting of N and Dl along the apico-basal axis at the exit of mitosis is important for proper N activation. We identified new regulators of N signaling following asymmetric cell division including membrane traffic regulators (AP-1) and regulators of epithelial cell cytokinesis (septins). We investigate the molecular mechanisms by which AP-1 and septins controls N signaling by studying: - novel AP-1 interacting factors and traffic regulators identified by genetic and biochemical means, - the role of AP- 1 on the transport of E-Cadherin (E-Cad), - the role of AP-1 and E-Cad in the organization of N signaling platform, - the remodeling of the junctions and the maintenance of epithelial cell polarity throughout ACD.  
 
==fundings==
Our research is currently funded by the CNRS, ANR Programme Blanc ApiNotch 2012-2015, La ligue Nationale contre le Cancer-Equipe Labellisée

Revision as of 00:45, 23 December 2014

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Research interests

Unequal segregation of Numb (red) in dividing SOP, tubulin (green)

Asymmetric cell division (ACD) is a conserved mechanism by which cell fate diversity is generated during development and throughout adult life. How a cell can produce two daughter cells with different identities and how defects in this asymmetry contribute to diseases are the fundamental questions we study using the Drosophila adult sensory organ (SO) lineage as a model system. SO Precursors (SOP) are epithelial cells present in a single layer neuroepithelium on the dorsal thorax of Drosophila. SOP undergoes a series of four ACD in which a mother cell gives rise to two daughter cells via uneven segregation of the Notch regulators Numb and Neuralized. Thus, at each division, the acquisition of cell identity is controlled by the differential activation of Notch. Notch is activated by Delta (Dl) present on the surface of adjacent cells. Our recent work contributed to show that sorting of N and Dl along the apico-basal axis at the exit of mitosis is important for proper N activation. We identified new regulators of N signaling following asymmetric cell division including membrane traffic regulators (AP-1) and regulators of epithelial cell cytokinesis (septins). We investigate the molecular mechanisms by which AP-1 and septins controls N signaling by studying: - novel AP-1 interacting factors and traffic regulators identified by genetic and biochemical means, - the role of AP- 1 on the transport of E-Cadherin (E-Cad), - the role of AP-1 and E-Cad in the organization of N signaling platform, - the remodeling of the junctions and the maintenance of epithelial cell polarity throughout ACD.

fundings

Our research is currently funded by the CNRS, ANR Programme Blanc ApiNotch 2012-2015, La ligue Nationale contre le Cancer-Equipe Labellisée