The extracellular protease AdamTS-B is a dosage-sensitive regulator of unicellular tracheal branch morphogenesis.

Epithelial tube morphogenesis requires coordinated interactions between epithelial cells and their extracellular environment, yet the extracellular mechanisms that regulate this process remain poorly understood. The Drosophila trachea provides an excellent model for investigating how extracellular remodeling contributes to epithelial tube morphogenesis. AdamTS-B, an extracellular ADAMTS protease, is expressed in the embryonic trachea from early to late stages of tracheal development. Loss of AdamTS-B caused mild defects in unicellular branch organization, whereas overexpression produced ectopic cyst-like structures. Additionally, AdamTS-B localized intracellularly and to basal protrusions of tracheal cells. Constitutively active EGFR phenocopied the AdamTS-B overexpression phenotype. Together, our findings identify AdamTS-B as a dosage-sensitive regulator of unicellular tracheal branch morphogenesis and support a model in which extracellular proteolysis contributes to epithelial tube architecture. The phenotypic similarity between AdamTS-B overexpression and constitutive EGFR activation further suggests a potential functional relationship between extracellular proteolysis and EGFR signaling during tracheal development.