Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
Department of Organismic and Evolutionary Biology, Museum of Comparative Zoology, Harvard University, Cambridge, MA 02138, USA.
Cell Rep. 2020 Sep 1;32(9):108098. doi: 10.1016/j.celrep.2020.108098.
Whole-body regeneration relies on the re-establishment of body axes for patterning of new tissue. Wnt signaling is required to correctly regenerate tissues along the primary axis in many animals. However, the causal mechanisms that first launch Wnt signaling during regeneration are poorly characterized. We use the acoel worm Hofstenia miamia to identify processes that initiate Wnt signaling during posterior regeneration and find that the ligand wnt-3 is upregulated early in posterior-facing wounds. Functional studies reveal that wnt-3 is required to regenerate posterior tissues. wnt-3 is expressed in stem cells, it is needed for their proliferation, and its function is stem cell dependent. Chromatin accessibility data reveal that wnt-3 activation requires input from the general wound response. In addition, the expression of a different Wnt ligand, wnt-1, before amputation is required for wound-induced activation of wnt-3. Our study establishes a gene regulatory network for initiating Wnt signaling in posterior tissues in a bilaterian.
全身再生依赖于身体轴的重建，以对新组织进行模式化。Wnt 信号在许多动物中沿着主轴正确再生组织是必需的。然而，在再生过程中首先启动 Wnt 信号的因果机制还描述不清。我们利用后生动物 Hofstenia miamia 来鉴定在尾部再生过程中启动 Wnt 信号的过程，发现配体 wnt-3 在朝向尾部的伤口中早期上调。功能研究表明 wnt-3 是再生尾部组织所必需的。wnt-3 在干细胞中表达，它是干细胞增殖所必需的，其功能是依赖于干细胞的。染色质可及性数据表明，wnt-3 的激活需要来自一般伤口反应的输入。此外，在截肢前表达另一种 Wnt 配体 wnt-1，对于诱导 wnt-3 的伤口激活是必需的。我们的研究建立了一个在两侧动物中启动尾部组织 Wnt 信号的基因调控网络。
