Blanc SVSE 2 - Blanc - SVSE 2 - biologie cellulaire et biologie du développement

Morphogenesis of proliferative epithelial tissue in Drosophila – MorphoDro

Morphogenesis of epithelial tissue by tumor supressor.

How proliferative tissues adopt their shape is a central and fascinating question in developmental biology. In the recent years, the Fat/Dachsous pathway has emerged as a conserved regulator in both vertebrates and invertebrates of tissue size and shape. Its function in the regulation of tissue size is well understood and underlies its tumour-suppressor activity. On the contrary, the understanding of its function in the regulation of tissue shape has remained sparse.

How tissue adopt their shape during development is a major challenge in biology.

1. We will describe and quantify tissue morphogenesis in correlation with the polarization of Dachs by implementing original quantitative methods in the field of tissue morphogenesis. <br />2. We will determine the role of Fj and Ds gradient in the control of tissue morphogenesis by combining classical genetic and innovative opto-genetic methods to modulate gene function locally and globally. <br />3. We will explore how cell bond tension imposed by the polarized distribution of Dachs impacts on the shape of groups of cells and on tissue morphogenesis, using a combination of time-lapse imaging, in situ stress measurement and modelling. <br />4. We will identify additional molecular partners of Dachs to understand how Dachs is polarized and how it regulates cortical tension, by combining biochemical and genetic approaches.

By a combination of methods (quantitative measurement of cell and tissue morphogenesis, genetics, opto-genetics, laser ablation, modelling), our aim is to implement an interdisciplinary approach to decipher the molecular mechanisms by which the Fat/Ds tumor suppressor pathway affects on the local mechanical cell properties to control global cell flows that shape epithelial tissues.

Collectively, our multi-scale imaging and measurements have provided us with an invaluable resource to investigate how signaling pathways control local cell mechanical properties to drive tissue morphogenesis (Bosveld et al., Science 2012 ). A second challenge is to measure in situ the tissue stress. We have implemented an innovative method based on large circular laser ablation to infer stress within tissue. Furthermore, in close collaboration with P. Marcq (UMR168), we have developed a spatial and temporal model of the relaxation of the tissue upon circular laser ablation. Thereby, we have analysed the respective contributions of tissue viscosity and friction in the yolk. Furthermore, our quantitative measurements and modelling revealed that tissue mechanics could be explored using continuum mechanics (Bonnet et al., JRSI, 2012}). Our circular ablation has more recently permitted to validate a non-invasive technique to measure mechanical stress in situ (collaboration with K. Sugimura and S. Ishihara, Kyoto University, Japan ; Ishihara, et al., 2013). This finding validates critical assumptions of our modelling of the contribution of the Fat/Ds/FJ planar polarity pathway in tissue morphogenesis (Bosveld et al., Science 2012).

The results obtained shape the future project of the team in term of undersatnd of tissue morphogenesis and the link between genetics and mechanics.

Degoutin JL, Milton CC, Yu E, Tipping M, Bosveld F, Yang L, Bellaiche Y, Veraksa A, Harvey KF. 2013. Riquiqui and Minibrain are regulators of the Hippo pathway downstream of Dachsous. Nat Cell Biol in press.
Heisenberg C-P. and Bellaïche 2013. Forces in tissue morphogenesis and patterning. Cell. 153:948-62.
Ishihara S, Sugimura K, Cox S.J, Bonnet I, Bellaiche Y, Graner F. 2013. Comparative study of non-invasive force and stress inference methods in tissue, Eur Phys J E Soft Matter. 36:45-55
Herszterg S, Liebfried A, Bosveld F, Martin C, Bellaiche Y. 2013. Interplay between the dividing cell and its neighbors regulates adherens junction formation during cytokinesis in epithelial tissue. Developmental Cell, 24: 256-70
Bosveld F, Bonnet I, Guirao B, Tlili S, Wang Z, Petitalot A, Marchand R, Bardet PL, Marcq P, Graner F, Bellaïche Y. 2012. Mechanical control of morphogenesis by Fat/Dachsous/Four-jointed planar cell polarity pathway. Science. 336:724-7.
Bonnet I, Marcq P, Bosveld F, Fetler L, Bellaïche Y, Graner F. 2012. Mechanical state, material properties and continuous description of an epithelial tissue. J R Soc Interface. 9:2614-23.

How proliferative tissues adopt their shape is a central and fascinating question in developmental biology. In the recent years, the Fat/Dachsous pathway has emerged as a conserved regulator in both vertebrates and invertebrates of tissue size and shape. Its function in the regulation of tissue size is well understood and underlies its tumour-suppressor activity. On the contrary, the understanding of its function in the regulation of tissue shape has remained sparse.

Using the epithelial tissue of the Drosophila pupa, our preliminary results have revealed a correlation between the local activation of the Fat/Dachsous and the global tissue morphogenesis. Furthermore we have shown that the Fat/Dachsous pathway triggers a local increase of cell bond tension in a specific region of the tissue; thereby identifying a putative link between the Fat/Dachsous pathway and mechanical cell properties.

Using a combination of methods (quantitative measurement of cell and tissue morphogenesis, genetics, opto-genetics, laser ablation, modelling), our aim is to implement an interdisciplinary approach to decipher the molecular mechanisms by which the Fat/Dachsous pathway affects on the local mechanical cell properties to control global cell flows that shape epithelial tissues.

The functions of the Fat/Dachsous pathway are conserved in multi-cellular organisms. Our findings will shed light on conserved mechanisms governing the coordination between proliferation and morphogenesis during development.

Project coordinator

Monsieur Yohanns Bellaiche (INSTITUT CURIE - SECTION DE RECHERCHE) – yohanns.bellaiche@curie.fr

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

Institut CURIE INSTITUT CURIE - SECTION DE RECHERCHE

Help of the ANR 392,760 euros
Beginning and duration of the scientific project: December 2011 - 36 Months

Useful links

Sign up for the latest news:
Subscribe to our newsletter