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Cell polarity is essential for the development of organisms. Our lab uses the Nematode C. elegans to study the establishment and the maintenance of polarity in various cell types. The team was created in 2007 with an Avenir INSERM starting grant and is focused on the interplay between cellular and developmental biology.
 
'''
== Current research ==
'''
 
Cell polarity is essential for the development of organisms. Our lab uses the Nematode ''C. elegans'' to study the establishment and the maintenance of polarity in various cell types. The team was created in 2007 with an Avenir INSERM starting grant and is focused on the interplay between cellular and developmental biology.
 


'''- Epithelial polarity maintenance and membrane traffic'''
'''- Epithelial polarity maintenance and membrane traffic'''


Epithelial cells rely on different intracellular trafficking pathways between the apical pole and the basolateral pole to achieve a polarised localisation of lipids and protein. Apical junctions act as a diffusion barrier separating the two poles. We study the role of the clathrin adaptor complex AP-1 in C. elegans epithelial cells. In C. elegans, as in Drosophila and mouse, the loss of AP-1 induces embryonic lethality. Our data suggest that this lethality is due to a new function of AP-1 in epithelial polarity maintenance (Shafaq-zadah et al., Development, in press).
Epithelial cells rely on different intracellular trafficking pathways between the apical pole and the basolateral pole to achieve a polarised localisation of lipids and proteins. Apical junctions act as a diffusion barrier separating the two poles. We found that in the ''C. elegans'' intestine the clathrin adaptor AP-1 is required for the apical localisation of several proteins including the polarity determinants CDC-42 and PAR-6 (Shafaq-Zadah et al., Development, 2012, 139:2061-70). In the epidermis, AP-1 together with clathrin, SOAP-1 and Rab11 controls the apical localisation of E-cadherin (Gillard et al, Development, 2015, 142:1684-94).  


Genetic data also show that AP-1 has a repressor role during the basolateral targeting of the EGF receptor in vulval epithelial cells. We have identified new genes implicated in that process. (Holmes et al., in prep).


'''- Polarity in the early embryo'''
'''- Polarity in the early embryo'''


The establishment of a polarity axis is essential for asymmetric cell division. At the one-cell stage C. elegans embryo, the asymmetric localisation of the conserved PAR proteins defines the anteroposterior axis of the embryo. Following this polarisation the embryo divides asymmetrically, giving rise to two daughter cells which adopt different fates. We are investigating the mechanisms that control polarity establishment.In particular we study PAR protein degradation (Pacquelet et al., 2008) as well as the links between polarity and membrane traffic.
The establishment of a polarity axis is essential for asymmetric cell division. At the one-cell stage ''C. elegans'' embryo, the asymmetric localisation of the conserved PAR proteins defines the anteroposterior axis of the embryo. Following this polarisation the embryo divides asymmetrically, giving rise to two daughter cells which adopt different fates. We are investigating the mechanisms that control polarity establishment. In particular we study PAR protein degradation (Pacquelet et al., 2008) and how polarity controls the positioning of the cytokinetic furrow (Pacquelet et al, submitted).
 
 
'''- Polarity in the intestine: from ''C. elegans'' to human diseases'''
 
In collaboration with Pr Frank Rümmele (group of Pr Nadine Cerf-Bensussan, Institut Imagine, Hôpital Necker-Enfants Malades), we exploit the results obtained in ''C. elegans'' to better characterise the defects observed in Microvillous Inclusion Disease, a rare intestinal disease (Michaux et al, submitted).
 
 
'''- Methodological developments: cryofixation/Tokuyasu hybrid method in ''C. elegans''
 
To improve immuno-electron microscopy in ''C. elegans'' we have developped a new method combining cryofixation/HPF) and cryosection/Tokuyasu (Nicolle et al, Traffic, in press).
 
 
 
'''Our research projects are supported by :'''
 
 
[[Image:Logo_FMR.png‎|200px]]  [[Image:LNCC35.gif‎|200px]]  [[Image:Logo_AVIESAN.jpg‎|200px]]

Revision as of 10:10, 6 May 2015

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Current research

Cell polarity is essential for the development of organisms. Our lab uses the Nematode C. elegans to study the establishment and the maintenance of polarity in various cell types. The team was created in 2007 with an Avenir INSERM starting grant and is focused on the interplay between cellular and developmental biology.


- Epithelial polarity maintenance and membrane traffic

Epithelial cells rely on different intracellular trafficking pathways between the apical pole and the basolateral pole to achieve a polarised localisation of lipids and proteins. Apical junctions act as a diffusion barrier separating the two poles. We found that in the C. elegans intestine the clathrin adaptor AP-1 is required for the apical localisation of several proteins including the polarity determinants CDC-42 and PAR-6 (Shafaq-Zadah et al., Development, 2012, 139:2061-70). In the epidermis, AP-1 together with clathrin, SOAP-1 and Rab11 controls the apical localisation of E-cadherin (Gillard et al, Development, 2015, 142:1684-94).


- Polarity in the early embryo

The establishment of a polarity axis is essential for asymmetric cell division. At the one-cell stage C. elegans embryo, the asymmetric localisation of the conserved PAR proteins defines the anteroposterior axis of the embryo. Following this polarisation the embryo divides asymmetrically, giving rise to two daughter cells which adopt different fates. We are investigating the mechanisms that control polarity establishment. In particular we study PAR protein degradation (Pacquelet et al., 2008) and how polarity controls the positioning of the cytokinetic furrow (Pacquelet et al, submitted).


- Polarity in the intestine: from C. elegans to human diseases

In collaboration with Pr Frank Rümmele (group of Pr Nadine Cerf-Bensussan, Institut Imagine, Hôpital Necker-Enfants Malades), we exploit the results obtained in C. elegans to better characterise the defects observed in Microvillous Inclusion Disease, a rare intestinal disease (Michaux et al, submitted).


- Methodological developments: cryofixation/Tokuyasu hybrid method in C. elegans

To improve immuno-electron microscopy in C. elegans we have developped a new method combining cryofixation/HPF) and cryosection/Tokuyasu (Nicolle et al, Traffic, in press).


Our research projects are supported by :