Systematic characterization of dorsal tracheal terminal cell branching throughout normal and dysregulated development in Drosophila larvae

Abstract

Biological transport networks deliver nutrients and oxygen to the cells and tissues of many organisms and display complicated morphologies that are difficult to describe mathematically. One example is the Drosophila larval tracheal system, a network of air channels which mediates gas exchange between the external environment and recipient cells. The finest level of this network consists of terminal cells, which have an intricate unicellular branched network. We present a statistical, longitudinal study of terminal cells in Drosophila larvae over all three stages of larval growth, during which the larvae dramatically increase their size. Scaling relations extracted from geometric features of terminal cell networks reveal how the growth strategy of terminal cells changes throughout development. We discovered that terminal cells exhibit stretching growth in the early larval stages and self-similar growth in the final larval stage. The presented statistical analyses are powerful tools for investigating structure-function relationships throughout biological network development. Future studies should confirm these findings using in vivo microscopy techniques. Lastly, we demonstrate that normal gene expression levels of two disease-relevant, gain-of-function mutations (the RASopathy-associated MEKF53S and melanoma-associated MEKE203K alleles) in the Ras signaling cascade bias tracheal cells toward the terminal cell fate.