What happens when Notum expression is knocked down in planaria?
Notum functions as localized brake on Wnt signaling at anterior-facing wounds producing microenvironment where Wnt ligands are deactivated. When Notum expression is knocked down by RNAi, inhibition absent, so wound retains high residual Wnt/beta-catenin activity normally reserved for posterior identity. High Wnt then imposes tail transcriptional program onto anterior blastema, leading to ectopic tail formation where head should regenerate, yielding two-tailed animals. Complete regeneration failure would require loss of stem cells, extra heads arise from beta-catenin depletion not elevation, normal regeneration depends on precise Notum mediated Wnt dampening to protect anterior fate from posteriorizing cues.
Ref: PNAS, Notum RNAi in planaria - excessive Wnt causes tail formation at anterior wound.