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Nadine H. Soplop
B.S., King’s College, Wilkes-Barre, PA - 1999
Thesis Advisor: Sunita G. Kramer, Ph.D.
Graduate Program in Cell and Developmental Biology
Robert Wood Johnson Medical School
Research Tower Room V-10
Thursday, August 11, 2011
The coordinated movement of cells is required to establish and maintain tissues during organogenesis. An emerging theme is that guidance molecules can orchestrate these coordinated movements, and play a general role in morphogenesis, but how they do this remains unclear. In this study we examine the function of the Slit-Robo family of guidance molecules in two tissues of differing complexity. We first examined the simple heart tube, formed when two rows of migrating heart cells contact each other and form a lumen at the embryonic dorsal midline. During heart formation, we found Slit-Robo is required to maintain adhesion between migrating heart cells in an early step of heart development. Slit-Robo are also required for cell shape changes leading up to and including the later step of heart development, lumen formation.
Next, we examined Slit-Robo signaling during the development of the large intestine of the Drosophila embryonic hindgut. The Drosophila embryonic hindgut has many levels of complexity that make it an attractive model to study Slit-Robo. For example, the hindgut epithelium is surrounded by a layer of visceral mesoderm, and these two tissues are co-dependent on each other during development. In addition, the lumen of large intestine is enclosed by three different cell types. We found that loss of robo does not disrupt overall hindgut patterning but results in lumen shape defects and a decrease in microvilli length on the boundary cells of the hindgut epithelium. While Robo normally acts locally to cause morphogenic changes, our results support a model where Robo signaling is required in the surrounding visceral mesoderm for correct microvilli length in the hindgut epithelium. These results establish a novel role for Robo signaling in regulation of microvilli growth and provide in vivo evidence for the role of the visceral mesoderm in controlling morphological changes in the underlying intestinal epithelium. Taken together, our findings support the theme that Slit-Robo play varied roles in morphogenesis, such as cell shape changes, regulation of adhesion and microvilli growth.