2025 Theses Doctoral

Biomechanical Regulation of Nascent Avian Foregut Growth and Elongation

Powell, Olivia Camille Shannon

The foregut tube gives rise to the lungs and upper gastrointestinal tract, enabling vital functions of respiration and digestion. How the foregut tube forms during embryonic development has historically received considerable attention, but over the past few decades this question has primarily been addressed indirectly through studies on morphogenesis of the primitive heart tube, a closely related process. As a result, many aspects of foregut development remain unresolved. Here, we exploit the accessibility of the chick embryo to study the initial formation of the foregut tube, combining embryology with fate mapping, live imaging, and biomechanical analyses.

The present study reveals that the foregut forms and elongates over a narrower time window than previously thought, and displays marked dorso-ventral and left-right asymmetries early in its development. Through tissue-specific ablation of endoderm along the anterior intestinal portal, we confirm its central biomechanical role in driving foregut morphogenesis, despite not directly contributing cells to the elongating tube. We further confirm the important role of this cell population in formation of the heart tube, with evidence that this role extends to later stages of cardiac looping as well. Finally, we investigate the role of Fibroblast Growth Factor-8 (FGF8) in regulating the actomyosin dynamics that drive foregut elongation.

Together, these data reveal the need for an intricate balance between intrinsic cell behaviors and extrinsic forces for normal foregut elongation, and set the stage for future studies aimed at understanding the underlying molecular cues that coordinate this balance. The work described in this dissertation ultimately aim to reveal the cellular and molecular mechanisms by which the endoderm folds from an epithelial sheet into a regionalized foregut tube, which is a fundamental aspect of establishing the vertebrate body plan.