Tissue absence initiates regeneration through Follistatin-mediated inhibition of Activin signaling

• Main Authors: Gavino, Michael A. (Contributor), Wenemoser, Danielle (Contributor), Wang, Irving E. (Contributor), Reddien, Peter (Contributor)
• Other Authors: Massachusetts Institute of Technology. Department of Biology (Contributor), Whitehead Institute for Biomedical Research (Contributor)
• Format: Article
• Language: English
• Published: eLife Sciences Publications, Ltd., 2014-03-20T16:23:33Z.
• Subjects: Article
• Online Access: Get fulltext

Regeneration is widespread, but mechanisms that activate regeneration remain mysterious. Planarians are capable of whole-body regeneration and mount distinct molecular responses to wounds that result in tissue absence and those that do not. A major question is how these distinct responses are activated. We describe a follistatin homolog (Smed-follistatin) required for planarian regeneration. Smed-follistatin inhibition blocks responses to tissue absence but does not prevent normal tissue turnover. Two activin homologs (Smed-activin-1 and Smed-activin-2) are required for the Smed-follistatin phenotype. Finally, Smed-follistatin is wound-induced and expressed at higher levels following injuries that cause tissue absence. These data suggest that Smed-follistatin inhibits Smed-Activin proteins to trigger regeneration specifically following injuries involving tissue absence and identify a mechanism critical for regeneration initiation, a process important across the animal kingdom.
National Institutes of Health (U.S.) (NIH (R01GM080639))
W. M. Keck Foundation
Howard Hughes Medical Institute (Early career scientist)