Collective cell migration is a defining feature of many morphogenetic processes.
Diseases such as congenital heart diseases and cancer arise due to mis-regulation of
collective migratory behaviour and animal models have played a pivotal role in dissecting
the molecular mechanisms which underlie this process. During embryonic heart
development, cardiac precursors undergo a stage of collective migration in both
vertebrates and invertebrates. We developed a paradigm to quantitatively assess collective
cell migration of cardiac precursors in live embryos of Drosophila, which is the simplest
genetic model organism with a heart. Therefore, we studied processes which are
commonly observed in most collective cell migration models such as guidance signalling
and extracellular matrix remodelling. Our results demonstrate that leading edge of
migrating cardioblasts is highly active and that this behaviour is regulated by guidance
cues, Slit and Netrin and their respective receptors Robo/Robo2 and Frazzled/Uncoordinated5.
These molecules cooperatively promote leading edge motility and epithelial
characteristics of the cardioblasts. Next, we determined that matrix restructuring around
the cardioblasts requires proteases Mmp1 and Mmp2, which are members of the highly
conserved Matrix Metalloproteinase family. We demonstrate that Mmp1 and Mmp2 have
distinct roles during lumen formation, however, both Mmp1 and Mmp2 are required for
collective motility of the cardioblast leading edge. Hence, we propose that embryonic
heart development in Drosophila is an effective and amenable model of collective cell
migration which can be applied to discover unique mechanisms which coordinate cell
movement in groups. / Thesis / Doctor of Philosophy (PhD)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/18265 |
| Date | 11 1900 |
| Creators | Raza, Qanber |
| Contributors | Jacobs, Roger, Biology |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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