STRIPAK Limits Stem Cell Differentiation of a WNT Signaling Center to Control Planarian Axis Scaling

Regeneration involves regulating tissue proportionality across considerable size ranges through unknown mechanisms. In planarians, which scale reversibly over 40× through regeneration, we identify the Striatin-interacting phosphatase and kinase (STRIPAK) complex as a potent negative regulator of axis length. Inhibition of two proteins in the STRIPAK complex, mob4 and striatin, dramatically increased posterior length, through expansion of a posterior wnt1+ signaling center within midline muscle cells. wnt1 was required for tail expansion after mob4 inhibition and dynamically reestablishes proportionality after amputation in normal animals, indicating STRIPAK represses Wnt signaling for scaling. Regulation of wnt1 expansion was stem cell dependent, demonstrating that control of signaling-center production through stem cell differentiation underlies proportional growth in adult regenerative tissue. Planarians must scale the relative size of tissues to accomplish regeneration. Schad and Petersen identify the mob4 and striatin components of the STRIPAK complex as negative regulators of tail size in planarians. STRIPAK acts by limiting stem cell differentiation of Wnt-expressing signaling-center cells that determine posterior scaling.