Planarian yorkie/YAP functions to integrate adult stem cell proliferation, organ homeostasis, and maintenance of axial patterning

During adult homeostasis and regeneration, the freshwater planarian must accomplish a constant balance between cell proliferation and cell death, while also maintaining proper tissue and organ size and patterning. Yet how these ordered processes are precisely modulated, remains relatively unknown. Here we show that planarians use the downstream effector of the Hippo signalling cascade, yorkie (yki; YAP in vertebrates) to control a diverse set of pleiotropic processes in organ homeostasis, stem cell regulation, regeneration, and axial patterning. We show that yki functions to maintain the homeostasis of the planarian excretory (protonephridial) system and to limit stem cell proliferation, while not affecting the differentiation process or cell death. Finally, we show that yki synergizes with WNT/β-catenin signalling to repress head determination by limiting the expression domains of posterior WNT genes and the WNT-inhibitor notum. Together, our data show that yki is a key factor in planarians that integrates stem cell proliferation control, organ homeostasis, and the spatial patterning of tissues.

在成体稳态与再生过程中，淡水涡虫（freshwater planarian）需在细胞增殖与细胞死亡之间维持动态平衡，同时保障组织与器官的尺寸及形态格局正常构建。然而，这些有序生物学过程的精确调控机制至今仍不甚明确。本研究发现，淡水涡虫借助Hippo信号通路级联的下游效应因子约克西（yorkie，简称yki；脊椎动物中同源蛋白为YAP），调控器官稳态、干细胞功能调控、再生过程及轴向格局构建等多效性生物学过程。研究表明，yki可维持淡水涡虫原肾型排泄系统（protonephridial system）的稳态，并抑制干细胞增殖，且不影响细胞分化与细胞死亡进程。最后，本研究证实yki可与WNT/β-连环蛋白（β-catenin）信号通路协同作用，通过限制后部WNT基因及WNT抑制剂notum的表达区域，抑制头部命运决定。综上，本研究数据表明，yki是淡水涡虫中整合干细胞增殖调控、器官稳态及组织空间格局构建的关键因子。