Tube formation, or tubulogenesis, is an elaborate form of epithelial morphogenesis that includes processes such as cell migration and cell shape changes. The embryonic Drosophila heart, or dorsal vessel, is an excellent model of tubulogenesis and more specifically the signaling mechanisms required for cell migration and lumen formation. Similar to vertebrate heart formation, Drosophila heart tubulogenesis begins with the collective migration of cardioblasts that meet at the midline and adhere at specialised junctions, enclosing a lumen between them. Roundabout, and its ligand Slit, are required to restrict cell-to-cell adhesions to the junctional domains of contralateral cardioblasts, as well as maintain the integrity of the lumen. The localisation patterns of Robo, and other luminal cell surface receptors important for lumen formation are significantly modified throughout heart formation. Initial receptor expression is broadly distributed over the cardioblast surface. Receptors are then relocalised to specific cell surface domains by late embryonic development. The mechanisms by which Robo and other cell surface receptors are localised have yet to be determined. Endocytosis is a promising mechanism by which cell surface receptors are targeted and trafficked to cell surface domains. Specifically, vesicular trafficking proteins, such as Rab GTPases, are molecular switches that regulate endocytic events. Here, we investigated the roles of Rab5, Rab11, and Sec6 during heart formation. Of these, only Rab5, a regulator of the early endosome, was required for lumen formation. Particularly, gain of function, loss of function, and overexpression of rab5 resulted in reduced lumen phenotype, characterised by lumen pockets rather than a continuous lumen along the anterior-posterior axis. Perturbed Rab5 function also resulted in the mislocalisation of Robo at the basal domain. Live imaging showed that expression of rab5 dominant negative, constitutively active, and overexpression constructs did not perturb apical membrane motility of migrating cardioblasts in the developing heart. / Thesis / Master of Science (MSc)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/25164 |
| Date | January 2019 |
| Creators | Perry, Katie L. |
| Contributors | Jacobs, J. Roger, Biology |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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