Fibronectin Regulates Wnt7a Signaling and Satellite Cell Expansion

SummaryThe influence of the extracellular matrix (ECM) within the stem cell niche remains poorly understood. We found that Syndecan-4 (Sdc4) and Frizzled-7 (Fzd7) form a coreceptor complex in satellite cells and that binding of the ECM glycoprotein Fibronectin (FN) to Sdc4 stimulates the ability of Wnt7a to induce the symmetric expansion of satellite stem cells. Newly activated satellite cells dynamically remodel their niche via transient high-level expression of FN. Knockdown of FN in prospectively isolated satellite cells severely impaired their ability to repopulate the satellite cell niche. Conversely, in vivo overexpression of FN with Wnt7a dramatically stimulated the expansion of satellite stem cells in regenerating muscle. Therefore, activating satellite cells remodel their niche through autologous expression of FN that provides feedback to stimulate Wnt7a signaling through the Fzd7/Sdc4 coreceptor complex. Thus, FN and Wnt7a together regulate the homeostatic levels of satellite stem cells and satellite myogenic cells during regenerative myogenesis.

Graphical AbstractFigure optionsDownload high-quality image (245 K)Download as PowerPoint slideHighlights
► Fzd7 and Sdc4 form a coreceptor complex in satellite cells
► FN stimulates Wnt7a activity through the Fzd7/Sdc4 coreceptor complex
► Activating satellite cells remodel their niche with FN
► FN regulates the satellite cell pool during muscle regeneration