MMPs and extracellular signaling



The follicle stem cells of the fly ovary generate the follicle epithelium, the somatic cells that cover the developing egg.  These stem cells are unusual in that they are far (about 50µm) from the apical cells that secrete stem-cell proliferative signals.  How do these proliferative signals, including the Wingless ligand, spread to reach the follicle stem cells?  We recently discovered that the GPI-anchored heparin sulfate proteoglycan Dally-like protein facilitates Wingless spreading to the follicle stem cells, and further, that Mmp2 cleaves Dlp to oppose the spreading of Wingless.  We are currently determining how other Wnt ligands are affected by Dlp in the germarium, where Mmp2 cleaves Dlp, and how Dlp is regulated. (Indrayani Waghmare, Bryan Cawthon)

Basement membrane dynamics

basement membrane.png                                             Green: basement membrane; red: gut peristalsis muscles
In collaboration with the Hudson, Bhave, and Vanacore labs at Vanderbilt, we recently demonstrated that basement membrane homeostasis and function is mediated by the extracellular enzyme peroxidasin and its necessary cofactor bromide.  In flies lacking bromide or lacking peroxidasin, the basement membrane becomes thickened and damaged.  We have found a similar thickening of the basement membrane occurs when it is damaged by a chemical agent, and we are using this chemical injury as a damage model to understand how basement membrane is repaired.  (Will Lewis, Angela Howard)

Wound healing

wound pic.png                               Calcium imaging (with GCaMP6m) around a laser wound.  

In most epithelial wounds, both the cell layer and the extracellular matrix (basement membrane) are damaged. To heal, cells at the wound margin must sense the wound, adopt a migratory front-rear polarity while maintaining their collective architecture, extend or migrate in the direction of the wound, and then re-establish a quiescent apical-basal polarity after the wound is closed.  How do epithelial cells coordinate these activities?   We are using a Drosophila epithelial model of wound healing because the tissue heals rapidly, within about half a day.  We collaborate with physicists in the laboratory of Shane Hutson (Vanderbilt Physics) to understand the signals that emanate from an epithelial wound and how the cells interpret these signals.  (James O'Connor, Will Lewis)