Activin signaling controls a wound-induced program essential for regenerative patterning

Abstract

A central problem in animal regeneration is how animals determine what body part to regenerate. Planarians are flatworms that can regenerate any missing body part, and are studied to identify mechanisms underlying regeneration. At transverse amputation planes, a poorly understood mechanism specifies regeneration of either a head or a tail. This head-versus-tail regeneration decision-making process is referred to as regeneration polarity and has been studied for over a century to identify mechanisms that specify what to regenerate. The Wnt antagonist gene notum is induced within hours after injury robustly at anterior-facing wounds preferentially, where it specifies head regeneration. We report that Activin signaling is required for regeneration polarity, and the underlying asymmetric activation of notum preferentially at anterior-facing wounds. We propose Activin signaling is involved in regeneration-specific responses broadly in the animal kingdom. Planarian patterning requires signaling from specific subsets of muscle cells. Furthermore, several of these subsets have been shown to express specific transcription factors, for which inhibition results in specific patterning phenotypes. Muscle heterogeneity and function in regeneration can be further studied through optimized single-cell sequencing datasets. We report an improved 10x -based planarian muscle cell scRNA-seq dataset that predicts novel transcription factors associated with muscle cell heterogeneity.