Differential control of Yorkie activity by LKB1/AMPK and the Hippo/Warts cascade in the central nervous system.
The Hippo (Hpo) pathway is a highly conserved tumor suppressor network that restricts developmental tissue growth and regulates stem cell proliferation and differentiation. At the heart of the Hpo pathway is the progrowth transcriptional coactivator Yorkie [Yki-Yes-activated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ) in mammals]. Yki activity is restricted through phosphorylation by the Hpo/Warts core kinase cascade, but increasing evidence indicates that core kinase-independent modes of regulation also play an important role. Here, we examine Yki regulation in the Drosophila larval central nervous system and uncover a Hpo/Warts-independent function for the tumor suppressor kinase liver kinase B1 (LKB1) and its downstream effector, the energy sensor AMP-activated protein kinase (AMPK), in repressing Yki activity in the central brain/ventral nerve cord. Although the Hpo/Warts core cascade restrains Yki in the optic lobe, it is dispensable for Yki target gene repression in the late larval central brain/ventral nerve cord. Thus, we demonstrate a dramatically different wiring of Hpo signaling in neighboring cell populations of distinct developmental origins in the central nervous system.
['Gailite|Ieva|I|', 'Aerne|Birgit L|BL|', 'Tapon|Nicolas|N|']
D000091162:AMP-Activated Protein Kinase Kinases D055372:AMP-Activated Protein Kinases D000818:Animals D030801:Animals, Genetically Modified D001921:Brain D049109:Cell Proliferation D002490:Central Nervous System D029721:Drosophila Proteins D004331:Drosophila melanogaster D020869:Gene Expression Profiling D018507:Gene Expression Regulation, Developmental D015971:Gene Expression Regulation, Enzymologic D005838:Genotype D047908:Intracellular Signaling Peptides and Proteins D007814:Larva D018613:Microscopy, Confocal D009687:Nuclear Proteins D011494:Protein Kinases D017346:Protein Serine-Threonine Kinases D013234:Stem Cells D015534:Trans-Activators D000091102:YAP-Signaling Proteins
Hippo stem cells development growth control neuroblast