Characterizing Segment-Dependent Robustness of Drosophila Tracheal Development

Abstract

The robustness of a developmental process is defined as the ability of a system to produce a consistent phenotype, despite high variability in input signals. This variability is often absorbed by signal pathways that temper the received signal into an “average” range, which keeps the system’s developmental trajectory leveled at wildtype phenotypes. When signal intensity exceeds the thresholds of this buffering effect, the system’s robustness breaks down, and development becomes disordered. Studying developmental robustness in the Drosophila melanogaster tracheal system has many applications to understanding how human developmental disorders occur. Drosophila tracheal development is dependent upon the FGF/FGFR signaling pathway. By perturbing tracheal development through the use of a heterozygous FGF background, terminal cell specification was discovered to be differentially sensitive to decreases in FGF ligand across metameres of the animal. Additionally, a novel FGFR activity sensor was confirmed to accurately identify active FGFRs. This sensor showed that FGFR activity levels across metameres correlate with these newly found differential metameric rates of terminal cell specification, the differentiation event controlled by FGFR activity. A model was constructed to show how developing tracheal metameres closer to the spiracles of the animal receive less FGF-dependent FGFR activity than metameres closer to the center of the animal. This makes them more susceptible to failure at specifying a terminal cell than middle metameres. This study demonstrates how robustness can fluctuate within the same developing system, leading to areas of the organism that are more prone to fail in achieving proper development.