Follistatin antagonizes activin signaling and acts with notum to direct planarian head regeneration

RH Roberts-Galbraith… - Proceedings of the …, 2013 - National Acad Sciences
Proceedings of the National Academy of Sciences, 2013National Acad Sciences
Animals establish their body plans in embryogenesis, but only a few animals can
recapitulate this signaling milieu for regeneration after injury. In planarians, a pluripotent
stem cell population and perpetual signaling of polarity axes collaborate to direct a steady
replacement of cells during homeostasis and to power robust regeneration after even severe
injuries. Several studies have documented the roles of conserved signaling pathways in
maintaining and resetting axial polarity in planarians, but it is unclear how planarians …
Animals establish their body plans in embryogenesis, but only a few animals can recapitulate this signaling milieu for regeneration after injury. In planarians, a pluripotent stem cell population and perpetual signaling of polarity axes collaborate to direct a steady replacement of cells during homeostasis and to power robust regeneration after even severe injuries. Several studies have documented the roles of conserved signaling pathways in maintaining and resetting axial polarity in planarians, but it is unclear how planarians reestablish polarity signaling centers after injury and whether these centers serve to influence identity decisions of stem cell progeny during their differentiation. Here we find that a planarian Follistatin homolog directs regeneration of anterior identity by opposing an Activin/ActR-1/Smad2/3 signaling pathway. Follistatin and Notum, a Wnt inhibitor, are mutually required to reestablish an anterior signaling center that expresses both cues. Furthermore, we show that the direction of cells down particular differentiation paths requires regeneration of this anterior signaling center. Just as its amphibian counterpart in the organizer signals body plan and cell fate during embryogenesis, planarian Follistatin promotes reestablishment of anterior polarity during regeneration and influences specification of cell types in the head and beyond.
National Acad Sciences