Department of Genetics, Microbiology and Statistics, Universitat de Barcelona (UB) & Institute of Biomedicine of Universitat de Barcelona (IBUB), Barcelona, Spain.
School of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich, UK.
Nat Commun. 2023 Jan 18;14(1):298. doi: 10.1038/s41467-023-35937-y.
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.
为了实现成功的再生，缺失组织的身份必须根据预先存在的组织来指定。水螅是研究这个过程背后机制的理想模型；同一区域的细胞可以根据缺失的身体部位再生头部或尾部。截肢后，Wnt/β-catenin 信号的差异激活指定了前后身份。最初，wnt1 和 notum（Wnt 抑制剂）在所有伤口中都表达，但 48 小时后，它们通过未知机制分别局限于后部或前部伤口。在这里，我们表明，截肢后 12 小时，根据预先存在的组织的极性，伤口区域细胞的染色质可及性以 Wnt/β-catenin 依赖的方式发生变化。基因组分析表明，同源盒转录因子和染色质重塑蛋白是 Wnt/β-catenin 的直接靶标，它们触发了后部效应物的表达。最后，我们确定 FoxG 是 wnt1 的上游调节剂，可能通过结合其第一内含子增强子区域。
