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Significance The correct regulation of tissue growth in developing organisms is essential for functional organ formation. The evolutionarily conserved transcriptional coactivator Yorkie (Yki)/Yes-activated protein (YAP) responds to a variety of upstream inputs to promote tissue growth. Yki/YAP is known to regulate stem cell proliferation, thus affecting final organ size. The Hippo (Hpo)/Warts kinase cascade is a key inhibitor of Yki activity in many epithelial tissues. Here, we show that Yki is inhibited by the nutrient-sensing liver kinase B1 (LKB1)/AMP-activated protein kinase (AMPK) cascade independent of Hpo/Warts in a population of neural progenitors in the developingDrosophila larval brain. Our results suggest a tissue-specific nutrient-dependent mode of Yki activity regulation. Furthermore, a tissue-specific differential wiring of Hpo signaling could represent an adjustment to the proliferation requirements of different tissue types.

Differential control of Yorkie activity by LKB1/AMPK and the Hippo/Warts cascade in the central nervous system