The Role of MMP2 in Drosophila melanogaster Fat Body Remodeling

Abstract

Matrix metalloproteinases are enzymes involved in important tissue remodeling mechanisms in many animal systems, including mammalian. They are required for scar resorption during wound healing, and are believed to also influence inflammation and re-epithelialization. MMPs work by loosening ECM contacts between cells at the wound edge, allowing uninjured cells behind the edge to proliferate and cover the damaged tissue (Gill and Parks, 2008). The proteases also take part in metastatic activity of tumor cells because they degrade the ECM of tumor cells, allowing them to detach and migrate to other parts of the body (Sato et al, 2005). In Drosophila, Matrix metalloproteinase 2 (MMP2) plays a vital role in tissue remodeling and programmed cell-death during metamorphosis (Page-McCaw, 2008). The larval fat body of Drosophila develops in the larva during the beginning stages of its life. This organ stores nutrients that power the animal through the non-feeding periods of its life, including metamorphosis. Metamorphosis is triggered by a pulse of 20-hydroxyecdysone (20E), which induces pupariation. 20E controls expression of dBlimp-1, a rapidly degrading protein that transcriptionally represses ßftz-f1. As the 20E titer declines, dBlimp-1 is degraded and the ßFTZ-F1 transcription factor is expressed (Agawa et al., 2007). ßFTZ-F1 functions as a nuclear receptor and confers competence upon tissues to be able to respond to a second pulse of 20E. MMP2 is expressed during the second pulse of 20E, and cleaves proteins in the ECM, enabling fat body cells to migrate. This second pulse induces the prepupal to pupal transition (Woodard et al., 1994). It has been shown that ßftz-f1 is necessary and sufficient to induce fat body remodeling in the presence of 20E. Without MMP2, the larval fat body fails to dissociate, and the transition does not occur normally (Bond, 2011). I am examining the regulation of MMP2 expression in larval fat body remodeling in D. melanogaster. I am testing the hypothesis that ßftz-f1 is necessary for the induction of MMP2 transcription by 20E in the late prepupa. I used transgenic flies to overexpress dBlimp-1 in the larval fat body, and examined the expression of MMP2 in the transgenic fat body compared to controls.