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Christian Dahmann
Control of epithelial morphogenesis
Previous and current research
During animal development epithelia undergo morphogenetic changes to produce their final shape and form. Many of these changes are driven by alterations in the adhesive and cytoskeletal properties of individual cells. We are studying how developmental signals interface with adhesion and cytoskeleton-associated molecules to control morphogenetic processes.
The control of epithelial cell shape by the Dpp/TGF-β signaling molecule
Cells of the developing Drosophila wing epithelium undergo profound shape changes. We have recently shown that signaling by Dpp, once thought to maintain cell survival, helps to control epithelial cell shape and organization. We are currently devising genetic screens to identify molecules that act downstream of Dpp signaling to control cell shape.
The Dpp signaling activity gradient correlates with the strength of an apical microtubule network in cells. Cross-section through a developing Drosophila wing epithelium. Cells in the center of the disc have high Dpp signaling activity (large triangle), whereas cells in the periphery, labelled in red, display little, if any, Dpp signaling activity (small triangles). Microtubules are shown in green. Apical of the columnar cells is to the top.
The control of epithelial cell sorting by the Hedgehog signaling molecule
The subdivision of tissues into non-intermingling sets of cells termed compartments is important for growth and patterning. We have previously shown that the sorting of cells at the boundary between anterior and posterior compartments of the developing Drosophila wing is controlled by a transcriptional response to the Hedgehog signaling molecule. Recent physical approaches, including the ablation of bonds between cells using laser light, have revealed that mechanical tension on cell bonds is elevated along this anterior-posterior compartment boundary. Computer simulations show that a local increase of cell bond tension suffices to maintain straight interfaces between compartments. Our results suggests a sorting mechanism by which an increased cell bond tension guides the rearrangement of cells after cell division to maintain straight and sharp compartment boundaries.
A Drosophila fly expressing GFP under control of the engrailed enhancer in all cells of the posterior compartments. Note the straight borders between GFP expressing and non-expressing cells, which coincide with compartment boundaries.
Future prospects and goals
- Identification of molecules acting downstream of Dpp signaling to control epithelial cell shape by genetic screens
- Identification of genes regulated by Hedgehog signaling in the developing wing
- Investigating the dynamics of cell sorting at compartment boundaries by real-time in vivo imaging of developing wings
- Analyzing the role of non-classical cadherins in epithelial morphogenesis
About
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Selected publications
Landsberg, K. P., Farhadifar, R., Ranft, J., Umetsu,
D., Widmann, T. J., Bittig, T., Said, A., Jülicher, F., and Dahmann, C. (2009): Increased
cell bond tension governs cell sorting at the Drosophila anteroposterior compartment boundary. Current Biology,
19, 1950-1955.
Viktorinova, I., König, T., Schlichting, K., and Dahmann, C. (2009): The cadherin Fat2 is required for planar cell polarity in the Drosophila ovary, Development, 136, 4123-4132.
Shen, J. and Dahmann, C. (2005): Extrusion of cells with inappropriate Dpp signaling from Drosophila wing disc epithelia. Science, 307, 1789-90.
Dahmann, C. and Basler, K. (2000): Opposing transcriptional outputs of Hedgehog signaling and engrailed control compartmental cell sorting at the Drosophila A/P boundary. Cell, 100, 411-422
Dahmann, C. and Basler, K. (1999): Compartment boundaries: at the edge of development. Trends in Genetics, 15, 320-326