Wnt7a activates the planar cell polarity pathway to drive the symmetric expansion of satellite stem cells.

Satellite cells in skeletal muscle are a heterogeneous population of stem cells and committed progenitors. We found that quiescent satellite stem cells expressed the Wnt receptor Fzd7 and that its candidate ligand Wnt7a was upregulated during regeneration. Wnt7a markedly stimulated the symmetric expansion of satellite stem cells but did not affect the growth or differentiation of myoblasts. Silencing of Fzd7 abrogated Wnt7a binding and stimulation of stem cell expansion. Wnt7a signaling induced the polarized distribution of the planar cell polarity effector Vangl2. Silencing of Vangl2 inhibited Wnt7a action on satellite stem cell expansion. Wnt7a overexpression enhanced muscle regeneration and increased both satellite cell numbers and the proportion of satellite stem cells. Muscle lacking Wnt7a exhibited a marked decrease in satellite cell number following regeneration. Therefore, Wnt7a signaling through the planar cell polarity pathway controls the homeostatic level of satellite stem cells and hence regulates the regenerative potential of muscle.