STRIPAK Limits Stem Cell Differentiation of a WNT Signaling Center to Control Planarian Axis Scaling
STRIPAK Limits Stem Cell Differentiation of a WNT Signaling Center to Control Planarian Axis Scaling
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DOI：
10.1016/j.cub.2019.11.068
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发表时间：
2019-12
期刊：
影响因子：
9.2
通讯作者：
Erik G. Schad;Christian P. Petersen
中科院分区：
文献类型：
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作者：
Erik G. Schad;Christian P. Petersen
再生涉及通过未知机制在相当大的尺寸范围内调节组织比例。在涡虫中，通过再生可可逆地扩大40倍以上，我们发现纹状蛋白相互作用磷酸酶和激酶（STRIPAK）复合物是轴长度的有效负调节因子。抑制STRIPAK复合体中的两个蛋白，mob4和striatin，通过扩大中线肌细胞内的后wnt1+信号中心，显著增加后长度。在正常动物中，在mob4抑制后，wnt1是尾巴扩张所必需的，而在截肢后，wnt1又动态地重建了尾巴的比例，这表明STRIPAK抑制Wnt信号以实现扩张。wnt1扩增的调控依赖于干细胞，这表明通过干细胞分化控制信号中心的产生是成体再生组织成比例生长的基础。
Regeneration involves regulating tissue proportionality across considerable size ranges through unknown mechanisms. In planarians, which scale reversibly over 40× through regeneration, we identify the Striatin-interacting phosphatase and kinase (STRIPAK) complex as a potent negative regulator of axis length. Inhibition of two proteins in the STRIPAK complex,mob4andstriatin, dramatically increased posterior length, through expansion of a posteriorwnt1+signaling center within midline muscle cells.wnt1was required for tail expansion aftermob4inhibition and dynamically reestablishes proportionality after amputation in normal animals, indicating STRIPAK represses Wnt signaling for scaling. Regulation ofwnt1expansion was stem cell dependent, demonstrating that control of signaling-center production through stem cell differentiation underlies proportional growth in adult regenerative tissue.