Institute Seminar – January 18th Christos Samakovlis: The molecular basis of airway maturation in Drosophila

The molecular basis of airway maturation in Drosophila

The respiratory tubes of mammalian lungs and the Drosophila tracheal system undergo a series of maturation events at the end of embryogenesis. During this period the nascent tubes acquire their mature size, clear the luminal liquid and transform into functional respiratory networks. We have recorded three precisely controlled transitions of cellular activities during airway maturation in living fly embryos: First, a secretion burst deposits extracellular matrix into the lumen and expands tube diameter. Second, the activation of a massive apical endocytosis wave clears the matrix. Finally, luminal liquid is evacuated and the network is filled with a gas within ten minutes. We have characterized several genes required for each maturation step, but the mechanisms underlying the precise spatial and temporal regulation of epithelial activities during airway maturation are unknown.

To address the regulation of airway maturation we used a tracheal specific driver and ~20000 transgenic UAS-RNAi strains to first identify all protein-coding genes involved in the process. We identified 1461 genes, involved in tube maturation. Tracheal inactivation of 1935 of the remaining genes caused lethality or adult phenotypes in >50% of the animals. We used GOstat to find overrepresented classes of biological gene ontologies among the 1461 genes in the tube maturation group. Genes involved in transport of proteins or ions, epithelial junction assembly, cytoskeletal organization, metabolic processes and RNP biogenesis are enriched in this set. Our main interest is to identify the developmental regulators of airway maturation. We classified 1172 “tube maturation” genes according to the molecular function annotation of the predicted proteins and the potential presence of H.sapiens and lack of C.elegans orthologs. This analysis identified 64 genes encoding proteins of unknown function (48), transcription factors (10), kinases (4), GPCR (1) and channels (1). I will present a new gene regulatory network that controls tube planar cell polarity, and integrity during airway liquid clearance.

Speaker invited by Tor Erik Rusten, Dept. of Biochemistry

Link:
Home page of the Christos Samakovlis lab