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

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. Overall design: RNA deep sequencing (RNAseq) was performed on whole uninjured animals 6 days following 3 RNAi feedings (3fd6) for control(RNAi) and yki(RNAi). Experiments were performed in biological-triplicate, sequenced to a depth of 50 million reads per sample, and multiplexed on an Illumina HiSeq2500 with 50 basepair, single-end reads.