Matrix Pathology Group

Research at the Matrix Pathology Group

Type IV collagen is proposed to be a key molecule in the evolvement of multicellular animals by forming the architectural unit basement membrane, a specialized form of the extracellular matrix. Functions of the basement membrane include guiding organ regeneration, tissue repair, modulation of cell differentiation, apical–basal polarity identification, cell migration and adhesion, regulation of growth factor signaling gradients, maintenance of tissue architecture and compartmentalization. Type IV collagenopathy is a devastating systemic disease affecting the circulatory, central nervous, renal and visual systems and the skeletal muscles. It is observed in patients carrying mutations predominantly in the COL4A1 gene, while documented phenocopies associated with mutations in the COL4A2 gene are less. The encoded proteins are components of the ubiquitous basement membrane in mammals. Col4a1 mouse mutants recapitulate the human symptoms of type IV collagenopathy. We chose the Drosophila melanogaster model as we recorded dominant, temperature-sensitive mutations in the cognate col4a1 gene of the fruit fly and demonstrated phenotypic elements which have not yet been explored in humans or in mouse models, as the antimorph, dominant-negative col4a1 mutations are lethal, a condition which cannot be maintained in mammals.