Contribution
of desmosomal cadherins to tissue homeostasis of intestine and liver
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The
dynamic relationship between cell adhesion, differentiation and
proliferation is of paramount importance for tissue homeostasis.
Desmosomes are prominent adhesion sites in epithelial tissues mediating
mechanical stability by anchoring the keratin intermediate filament
cytoskeleton. In addition, it has been suggested that desmosomal
components contribute to cell differentiation and participate in growth
regulation. To test the various desmosomal functions in vivo, we have
generated transgenic mice that allow temporally-defined and cell
type-restricted depletion of the desmosome-specific cell-cell adhesion
molecule desmoglein 2 either in enterocytes or hepatocytes. The goal of
the project is to understand how the loss of desmoglein 2 affects
desmosome formation and, more importantly, how compromised desmosomal
adhesion influences the properties and dynamic behaviour of cell types
with either low or high proliferative activity (i.e., enterocytes and
hepatocytes, respectively) in health and disease. To this end, we will
compare clinical features, histopathology, cell adhesion, cytoskeletal
organisation, growth, and gene transcription in mice lacking desmoglein
2 in the intestine and liver. In addition, using chemical and genetic
tumor models we will determine how the altered phenotypes affect tissue
reactivity, tumor growth, tumor differentiation, and malignant
transformation.
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Principal
investigator: Prof. Dr. Rudolf Leube Funding:
DFG
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