Date of Award

2018

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Graduate Group

Cell & Molecular Biology

First Advisor

Amin S. Ghabrial

Abstract

Biological tubes adopt a variety of shapes to carry out their functions. In addition to multicellular tubes, single epithelial or endothelial cells build unicellular lumens lined by an apical membrane devoid of cell junctions, or seams. Such seamless tubes are highly conserved from invertebrates to vertebrate organs, but the factors regulating their formation and maintenance remain poorly understood in any system. Using a forward genetic approach in the Drosophila tracheal (respiratory) system, we have characterized a mutant called ichor, which compromises the integrity and shape of seamless tubes in tracheal terminal cells. We demonstrate that Ichor promotes seamless tube integrity and shape by transcriptionally activating genes required to assemble an extracellular matrix (cuticle) lining the lumens of terminal cells. The cuticle has long been thought function as a passive exoskeleton, but this work demonstrates that the cuticle contains signals regulating seamless tube growth and/or maintenance. All tubes are lined by apical extracellular matrices, but their composition, assembly, and functions are poorly understood. By characterizing effectors acting downstream of Ichor, we can systematically identify factors controlling all three processes in a model lumenal matrix.

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