Cell signaling networks in polarised tissue establishment and remodeling
During tissue morphogenesis the individual cell architecture is profoundly reorganized to promote shape changes, to exchange neighbours or to become motile. The cellular events that occur during morphogenesis provide paradigms that advance our understanding of abnormal cell behaviour in human diseases.
We are using Drosophila as a model to study molecular mechanisms crucial for morphogenetic movements of epithelial cells. Cleavage of Drosophila embryos serves as a paradigm to study mechanisms required for the generation of polarized epithelial cells (Figure 1).
During gastrulation a subpopulation of epithelial cells, the presumptive mesoderm, undergoes an epithelial to mesenchymal transition (EMT) (Figure 2). We established that signalling through fibroblast-growth-factors is essential to trigger cell shape changes of mesoderm cells and identified two novel homologues of the FGF8/17/18 subfamily. Our focus of research is to understand how FGF-signalling controls complex cell rearrangements in the embryos and which molecular interactions lead to changes in cell adhesion and the cytoskeleton in the responding cells. A first handle of this problem is provided by our identification of the Rho guanine nucleotide exchange factor Pebble, the fly homologue of the human proto-oncogene ect2, as an essential component of this signalling pathway.
Figure 1- Confocal sections of an embryo during progression of cell formation. Plasma membrane (Neurotactin; green), adherens junctions (Armadillo/ß-catenin; red), nuclei (DNA; blue).
Figure 2- EMT during Drosophila gastrulation. Top row: cartoon of embryo cross sections (ectoderm red; mesoderm green). Middle row: mesoderm cells expressing a transgenic membrane marker (twi::CD2: red; Twist; green). Lower row: confocal optical sections. Phase 1 (‘tube’): mesoderm epithelial tube attached to ectoderm. Phase 2 (‘migration’) disintegration of epithelial tube and loss of epithelial polarity. The migrating cells form a leading edge and extend protrusions into the direction of their migration. Phase 3 (‘termination’) the mesoderm has adopted a monolayer configuration.
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