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Long-range signaling to stem cells

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Two factors – Dlp and Mmp2 – regulate the proliferation of follicle stem cells in the fruit fly ovary, Vanderbilt researchers report in the Sept. 29 Journal of Cell Biology.

Xiaoxi Wang, Ph.D., and Andrea Page-McCaw, Ph.D. found that Dlp, a glypican protein, helps the signaling protein Wingless (Wg) spread from the cells where it is produced to the follicle stem cells located about five cell diameters away.

They demonstrated that Mmp2, a matrix metalloproteinase (MMP), opposes Dlp-mediated spreading of Wg to the stem cells. Mmp2 cleaves Dlp and causes it to relocalize inside the cell, where it can no longer interact with Wg. Mmp2-deficient ovaries had increased Wg distribution, activity and stem cell proliferation.

The system could allow for spatial control of Wg signaling to targets at different distances from the source, the researchers conclude.

Mammalian MMPs can both promote and suppress tumorigenesis. The current studies showing that Mmp2 inhibits stem cell proliferation may advance understanding of the protective roles of MMPs in cancer.

This research was supported by grants from the National Institutes of Health (HD074834, GM073883).

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