title: Tissue absence initiates regeneration through follistatin-mediated inhibition of activin signaling.
abstract: 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. DOI:http://dx.doi.org/10.7554/eLife.00247.001.
authors.affiliation: Department of Biology , Howard Hughes Medical Institute, Whitehead Institute, Massachusetts Institute of Technology , Cambridge , United States.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Gaviño
authors.forename: Danielle
authors.initials: D
authors.lastname: Wenemoser
authors.forename: Irving E
authors.initials: IE
authors.lastname: Wang
authors.forename: Peter W
authors.initials: PW
authors.lastname: Reddien
mesh_terms: D028341:Activins / Q000378:metabolism*; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D038681:Follistatin / Q000235:genetics / Q000378:metabolism*; D005838:Genotype; D010641:Phenotype; D034622:RNA Interference; D012038:Regeneration; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism; D013997:Time Factors; D014945:Wound Healing
chemical_list: D029742:Caenorhabditis elegans Proteins; D038681:Follistatin; D028341:Activins
keywords: Activin; Follistatin; Other; planarian regeneration; wound signaling
references.citation: Development. 2011 Oct;138(20):4387-98
references.pmid: 21937596
references.citation: Science. 2005 Nov 25;310(5752):1327-30
references.pmid: 16311336
references.citation: Annu Rev Cell Dev Biol. 2004;20:725-57
references.pmid: 15473858
references.citation: Bioinformatics. 2001 Aug;17(8):754-5
references.pmid: 11524383
references.citation: Dev Growth Differ. 2007 May;49(4):345-9
references.pmid: 17501910
references.citation: Dev Growth Differ. 2006 Aug;48(6):371-80
references.pmid: 16872450
references.citation: Dev Biol. 2010 Aug 15;344(2):979-91
references.pmid: 20599901
references.citation: Nat Rev Genet. 2002 Mar;3(3):210-9
references.pmid: 11972158
references.citation: Nucleic Acids Res. 1994 Nov 11;22(22):4673-80
references.pmid: 7984417
references.citation: Proc Natl Acad Sci U S A. 2009 Oct 6;106(40):17061-6
references.pmid: 19805089
references.citation: Mol Biol Evol. 2000 Apr;17(4):540-52
references.pmid: 10742046
references.citation: Mol Cell Endocrinol. 2004 Oct 15;225(1-2):127-32
references.pmid: 15451577
references.citation: Genome Biol. 2011 Aug 16;12(8):R76
references.pmid: 21846378
references.citation: PLoS One. 2007 Nov 28;2(11):e1227
references.pmid: 18043735
references.citation: Genes Dev. 2012 May 1;26(9):988-1002
references.pmid: 22549959
references.citation: Dev Dyn. 2009 Feb;238(2):443-50
references.pmid: 19161223
references.citation: Proc Natl Acad Sci U S A. 1988 Jul;85(14):5126-30
references.pmid: 3164865
references.citation: Dev Biol. 2010 Nov 1;347(1):24-39
references.pmid: 20707997
references.citation: Methods Mol Biol. 1994;25:307-18
references.pmid: 8004173
references.citation: Oncogene. 2005 Apr 21;24(18):3028-41
references.pmid: 15735717
references.citation: Proc Natl Acad Sci U S A. 2011 Aug 30;108(35):14560-5
references.pmid: 21841138
references.citation: Curr Biol. 2011 Feb 22;21(4):294-9
references.pmid: 21295483
references.citation: Cell. 1994 Apr 22;77(2):283-95
references.pmid: 8168135
references.citation: Dev Biol. 2007 Nov 1;311(1):79-94
references.pmid: 17905225
references.citation: Mol Cell Endocrinol. 2001 Jun 30;180(1-2):179-82
references.pmid: 11451589
references.citation: Science. 1990 Feb 16;247(4944):836-8
references.pmid: 2106159
references.citation: Curr Biol. 2011 Feb 22;21(4):300-5
references.pmid: 21295481
references.citation: Proc Natl Acad Sci U S A. 2013 Jan 22;110(4):1363-8
references.pmid: 23297191
references.citation: Dev Biol. 2010 Feb 1;338(1):76-85
references.pmid: 19766622
references.citation: Bioessays. 2000 Jun;22(6):578-90
references.pmid: 10842312
references.citation: Development. 2007 Nov;134(22):4043-51
references.pmid: 17942485
references.citation: Dev Biol. 1996 Feb 1;173(2):490-8
references.pmid: 8606007
references.citation: Science. 1987 Sep 11;237(4820):1333-6
references.pmid: 2442813
references.citation: Curr Biol. 2007 Aug 21;17(16):1390-5
references.pmid: 17683938
references.citation: Gastroenterology. 1995 Apr;108(4):1136-42
references.pmid: 7698581
references.citation: Am J Pathol. 2011 Aug;179(2):915-30
references.pmid: 21689628
references.citation: Bioinformatics. 2003 Aug 12;19(12):1572-4
references.pmid: 12912839
references.citation: Science. 2011 May 13;332(6031):811-6
references.pmid: 21566185
references.citation: Mech Dev. 2008 Jan-Feb;125(1-2):106-16
references.pmid: 18042353
references.citation: Dev Biol. 2008 Mar 1;315(1):203-16
references.pmid: 18234181
references.citation: Cell Rep. 2012 Aug 30;2(2):294-307
references.pmid: 22884275
references.citation: Dev Cell. 2005 May;8(5):635-49
references.pmid: 15866156
references.citation: Cell Stem Cell. 2008 Sep 11;3(3):327-39
references.pmid: 18786419