Genetic Dissection of Heart Development in the Fruit Fly Drosophila Melanogaster
| dc.contributor.advisor | Olson, Eric N. | en |
| dc.creator | Yi, Peng | en |
| dc.date.accessioned | 2010-07-12T18:03:35Z | |
| dc.date.available | 2010-07-12T18:03:35Z | |
| dc.date.issued | 2007-12-18 | |
| dc.description.abstract | The early morphogenetic mechanisms involved in heart formation are evolutionarily conserved. The Drosophila heart, known as the dorsal vessel, functions as a pulsatile tube-like organ containing an inner layer of contractile cardial cells that adhere tightly to an adjacent layer of pericardial cells. A genetic screen for genes that control Drosophila heart development revealed a cardiac defect in which pericardial and cardial cells dissociate causing loss of cardiac function and embryonic lethality. This phenotype resulted from mutations in the genes encoding HMG-CoA Reductase, downstream enzymes in the mevalonate pathway, and G-protein Ggamma 1, which is geranylgeranylated, thus representing an endpoint of isoprenoid biosynthesis. These findings reveal a cardial cell-autonomous requirement of Ggamma 1 geranylgeranylation for heart formation and suggest the involvement of the mevalonate pathway in congenital heart disease. In addition, we found that the heterotrimeric G proteins Gbeta 13F and G-oalpha 47A together with the RGS (regulator of G protein signaling) protein Loco function in the same pathway as Ggamma 1 to regulate septate junction formation in cardial cells of the Drosophila heart. We also present evidence that the septate junction protein Sinuous interacts with Pericardin, a matrix protein secreted by pericardial cells, providing the molecular basis for cardial-pericardial cell adhesion and serving as a mediator of the actions of the mevalonate pathway and heterotrimeric G protein signaling in Drosophila heart development. | en |
| dc.format.digitalOrigin | born digital | en |
| dc.format.medium | Electronic | en |
| dc.format.mimetype | application/pdf | en |
| dc.identifier.oclc | 759399923 | |
| dc.identifier.uri | https://hdl.handle.net/2152.5/437 | |
| dc.language.iso | en | en |
| dc.subject | Heart | en |
| dc.subject | Drosophila melanogaster | en |
| dc.subject | Genetic Testing | en |
| dc.title | Genetic Dissection of Heart Development in the Fruit Fly Drosophila Melanogaster | en |
| dc.type | Thesis | en |
| dc.type.genre | dissertation | en |
| dc.type.material | Text | en |
| thesis.date.available | 2007-12-18 | |
| thesis.degree.department | Graduate School of Biomedical Sciences | en |
| thesis.degree.discipline | Genetics and Development | en |
| thesis.degree.grantor | UT Southwestern Medical Center | en |
| thesis.degree.level | Doctoral | en |
| thesis.degree.name | Doctor of Philosophy | en |