Formation of a tubular organ, such as the heart, requires cells to integrate positional and polarity signals in order to enclose a fluid or gas transporting lumen. Developing tubes must establish a site for lumen initiation, demarcate membrane domains, and modulate cell polarization and morphology. The Drosophila melanogaster embryonic heart is a mesodermal tube model displaying a unique polarity, reminiscent of vertebrate vasculature. We have characterized a role for the transmembrane adhesion receptor αPS3βPS1 integrin and its cytoplasmic adaptor Talin in heart tubulogenesis. βPS1 and Talin are early indicators of the luminal site and Talin-mediated integrin function is essential for cardioblast polarization and morphology prior to and during lumen development. Careful analysis of hearts in embryos homozygous for a null allele of rhea, the gene encoding Talin, reveals that Talin is required to correctly orient the heart cell polarity such that a continuous central open lumen is enclosed. Without proper integrin or Talin function, the luminal determinants Slit and its receptor Robo are not stabilized within the heart, a central lumen fails to form, and the midline is instead marked by continuous adhesion. Furthermore, although Talin is essential for proper βPS1 integrin localization within the heart, either of Talin’s two integrin binding sites are sufficient to stabilize βPS1 along the luminal domain and establish an open cardiac tube. Taken together, our findings reveal an instructive role for integrins and Talin in communicating polarization cues central to heart tubulogenesis. / Thesis / Doctor of Philosophy (PhD)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/15982 |
| Date | January 2014 |
| Creators | Vanderploeg, Jessica |
| Contributors | Jacobs, J. Roger, Biology |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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