Group Christos Samakovlis

Epithelial organogenesis in Drosophila

Branched tubular organs are found in most animals. They include tissues like the lung, kidney and the vascular system. Many of the basic principles of tube construction in these organs are conserved among species. We aim to describe the genetic programs leading to the formation of a functional epithelial tubular network. The Drosophila airways, the trachea, form a complex tubular system that delivers air directly to all tissues in the animal. Our work utilizes genetics, bioinformatics and live imaging in Drosophila to characterize the molecular control of tube size and epithelial organ maturation.

Tube maturation: From morphogenesis to function

The development of air-filled respiratory organs is crucial for survival. We have combined live imaging with genetics to dissect airway maturation. Initially, a secretion burst deposits proteins into the nascent tracheal tubes. Solid material is then rapidly cleared and shortly thereafter liquid is removed from the lumen. The mechanisms underlying the precise spatial and temporal regulation of epithelial activities during airway maturation are unknown. We have used a tracheal specific driver and ~20000 transgenic UAS-RNAi strains to first describe all protein-coding genes involved in the process. To identify the developmental regulators of airway maturation, we preselected about 600 genes encoding putative regulators and further classified these genes into 12 groups based on the defects in tube morphologies, apical secretion and protein clearance events caused by their tracheal inactivation. The combination of this phenotypic analysis with the data from protein interaction databases reveals new gene regulatory networks controlling airway maturation.

Grainy head in tube size control and wound healing

Grainy head (grh), is a phylogenetically conserved transcription factor. In grh mutants, the apical epithelial cell membrane is overgrown resulting in overgrown airway tubes. Except for its developmental function, Grh emerged as a major regulator of epidermal wound healing in vertebrates and flies. A major focus of our work is the functional analysis Grh target genes, which we recently identified by ChIP-seq. We are exploring their function in epithelial wound healing and airway tube size control.

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