Epithelial tube size regulation: the role of the apical extracellular matrix in the tracheal system of Drosophila melanogaster

• Applicant: Professor Dr. Stefan Luschnig
• Subject Area: Cell Biology
• Term: from 2005 to 2011
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 20292880

The establishment and maintenance of the proper dimensions (length and diameter) of epithelial tubes is strictly controlled and essential in many organs. Defects in tube size cause serious and widespread diseases, such as Polycystic Kidney Disease. However, the molecular mechanisms of tube size regulation are poorly understood. The Drosophila tracheal (respiratory) system consists of branched epithelial tubes, which transport gases within the body. This system allows powerful genetic and cell biological approaches and provides an accessible model for the far more complicated situation in vertebrates. We have found that a chitinous extracellular matrix accumulates in the tracheal lumen and is necessary for normal tube size and shape. However, very little is known about the protein components of this extracellular matrix, and how it is involved in tube size regulation. We identified two related apically secreted proteins, CLP1 and CLP2, which accumulate in the tracheal lumen and presumably act by deacetylating Chitin. Mutations in these genes result in excessive elongation of tracheal tubes. A functional analysis of the CLP proteins is proposed. The link between the extracellular matrix and regulation of apical membrane growth will be analyzed by genetic approaches, live imaging and ultrastructural analysis of wild type and mutant situations. A genetic approach is proposed to identify new genes involved in tube size regulation, including new lumenal components.

• DFG Programme: Research Grants
• International Connection: Switzerland