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.
Apoptosis and Proliferation Control Laboratory, The Francis Crick Institute, Lincoln's Inn Fields Laboratory, London WC2A 3LY, United Kingdom.
Ieva
I
Gailite
Apoptosis and Proliferation Control Laboratory, The Francis Crick Institute, Lincoln's Inn Fields Laboratory, London WC2A 3LY, United Kingdom.
Birgit L
BL
Aerne
Apoptosis and Proliferation Control Laboratory, The Francis Crick Institute, Lincoln's Inn Fields Laboratory, London WC2A 3LY, United Kingdom nic.tapon@crick.ac.uk.
Nicolas
N
Tapon
D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D030801:Animals, Genetically Modified; D001921:Brain / Q000196:embryology*; D049109:Cell Proliferation; D002490:Central Nervous System / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D005838:Genotype; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007814:Larva / Q000378:metabolism; D018613:Microscopy, Confocal; D009687:Nuclear Proteins / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology; D015534:Trans-Activators / Q000378:metabolism*; D000091102:YAP-Signaling Proteins; D000099317:Hippo Kinases
D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases; D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D015534:Trans-Activators; D000091102:YAP-Signaling Proteins; C503814:Yki protein, Drosophila; C495775:LKB1 protein, Drosophila; C499474:hpo protein, Drosophila; D000099317:Hippo Kinases
Hippo; development; growth control; neuroblast; stem cells