Wnt/β-catenin signalling is required for pole-specific chromatin remodeling during planarian regeneration

For successful regeneration, the identity of the missing tissue must be specified according to the pre-existing tissue. Planarians are ideal for the study of the mechanisms underlying this process; the same field of cells can regrow a head or a tail according to the missing body part. After amputation, the differential activation of the Wnt/β-catenin signal specifies anterior versus posterior identity. Initially, both wnt1 and notum (Wnt inhibitor) are expressed in all wounds, but 48 hours later they are restricted to posterior or anterior facing wounds, respectively, by an unknown mechanism. Here we show that 12 hours after amputation, the chromatin accessibility of cells in the wound region changes according to the polarity of the pre-existing tissue in a Wnt/β-catenin-dependent manner. Genomic analyses suggest that homeobox transcription factors and chromatin-remodeling proteins are direct Wnt/β-catenin targets, which trigger the expression of posterior effectors. Finally, we identify FoxG as a wnt1 up-stream regulator, probably via binding to its first intron enhancer region.E.P.-C. is a recipient of an FPI (Formación del Profesorado Investigador) scholarship from the Spanish Ministerio de Ciencia, Innovación y Universidades. S.C.-L. was a recipient of a FI-FDR fellowship 2017FI_B_00191 from AGAUR (Generalitat de Catalunya). M.M.-B was supported by the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme FP7 under REA grant agreement number 607142 (DevCom). M.M.-B also thanks the John and Pamela Salter Trust for funding support. E.S. and T.A. received funding from the Ministerio de Educación y Ciencia (grant number BFU2017-83755-P, BFU2014-56055-P and BFU2020-116372GB-I00). E.S. and T.A. benefit from 2017SGR-1455 from AGAUR (Generalitat de Catalunya). E.S. received funding from AGAUR (Generalitat de Catalunya: grant number 2014SGR687). J.L.G.-S. received funding from the ERC (Grant 944 Agreement No. 740041), the Spanish Ministerio de Economía y Competitividad (Grant No. 945 BFU2016-74961-P) and the institutional grant Unidad de Excelencia María de Maeztu (MDM946 2016-0687)