FAIRDOMHubModelsLutz Bruschhttps://fairdomhub.org/models/760?version=1Technische Universität DresdenFAIRDOMHubThe mechanisms of organ size control remain poorly understood. A key question is how cells collectively sense the overall status of a tissue. We addressed this problem focusing on mouse liver regeneration. Using digital tissue reconstruction and quantitative image analysis, we found that the apical surface of hepatocytes forming the bile canalicular network expands concomitant with an increase in F-actin and phospho-myosin, to compensate an overload of bile acids. These changes are sensed by the Hippo transcriptional co-activator YAP, which localizes to apical F-actin-rich regions and translocates to the nucleus in dependence of the integrity of the actin cytoskeleton. This mechanism tolerates moderate bile acid fluctuations under tissue homeostasis, but activates YAP in response to sustained bile acid overload. Using an integrated biophysical-biochemical model of bile pressure and Hippo signaling, we explained this behavior by the existence of a mechano-sensory mechanism that activates YAP in a switch-like manner. We propose that the apical surface of hepatocytes acts as a self-regulatory mechano-sensory system that responds to critical levels of bile acids as readout of tissue status.Bile canaliculi remodeling activates YAP via the actin cytoskeleton during liver regeneration.Meyer Kirstin K, Morales-Navarrete Hernan H, Seifert Sarah S, Wilsch-Braeuninger Michaela M, Dahmen Uta U, Tanaka Elly M EM, Brusch Lutz L, Kalaidzidis Yannis Y, Zerial Marino MRegenerations, YAP2, YAP65, COB1, Hippo, Hippo Signaling Pathways, Liver, DmelCG4005, NPIPA, Yap, YAP, NPIP, YY1AP, Yap65, Hippo Signaling, AI325207, Hippo Pathway, temporal, Liver., yap, morpheus, Signaling Pathway, HCCA1, HCCA2, CG4005, Regeneration, Liver Regenerations, Yki, YKI, Yorkie, activation, incidencebile capillary, Regenerations, biliary canaliculus, YAP2, YAP65, COB1, Liver, DmelCG4005, Yap, YAP, Canaliculus, Actin Microfilaments, YY1AP, Yap65, Actin, Filaments, AI325207, Bile Canaliculus, bile canaliculi, Filament, Actin Filament, Actin Filaments, Liver., Microfilament, yap, Cytoskeletons, HCCA1, HCCA2, CG4005, Regeneration, Liver Regenerations, Microfilaments, Yki, YKI, Cytoskeleton, Canaliculi, Yorkie, Actin Cytoskeletons, Actin Microfilament, BileSalts, YAP65, Bile Acids, Size, YY1AP, Bile Salt, Hepatocyte, beta-Actin, Yap65, sci, Atomkern, prevention, set of sense organs, Actin Activated, Bile salt, Cytoskeletons, Hepatic Cell, gamma Actin, horsetail nucleus, CG9063, AA959943, HOW, How, prevention and control, IKKg, l(3)j5D5, KEY, Key, integumentum commune, Bile, 24B, neuronal nucleus, nucleus atomi, N Actin, simple tissue., reference sample, Yap, YAP, Gallensaeuren, Tissue, Salt, stru, Myosin ATPase, Hippo Signaling, l(3)S053606, beta Actin, CG10293, BcDNA:GH03694, sense organs set, Acts, preventive measures, l(3)j5B5, Isoactin, Adenosinetriphosphatase, yap, N-Actin, Sludge, MHC16, Microfilaments, G-Actin, sense organ subsystem, Biliary Sludge, DmelCG9063, single-organism behavior, Acta-2, Bile Acid, 0904/17, preventive therapy, Liver, external covering of organism, Process, sensory organ system, NMHC-II-C, alpha Isoactin, Actin Activated ATPase, Bile Salts, Actsk-1, organism surface, Salvador-Warts-Hippo signaling pathway, Acceptance Processes, Hepatic Cells, DmIKKgamma, Acceptance Process, dIKK, SZ1, Signaling Pathway, Weight, HCCA1, Kenny, HCCA2, NMHC II-C, cell nucleus, simple tissue, 5beta-bile acid, Actin Microfilament, hippo signaling cascade, DFNA4, Acid, YAP2, BcDNAGH03694, IKK-gamma, Myosin Adenosine Triphosphatase, Actin, gamma-Actin, Filaments, Bile acid, Hippo Pathway, 3L6, DmelCG16910, sense organs, rich, integumentary system, Cells, Regeneration, Liver Regenerations, anon-EST:Liang-2.39, Acids, dermal system, sensory systems, DmelCG4005, noyau atomique, DFNA4A, Myosin Adenosinetriphosphatase, Processes, P62, number, bile acids, Kern, presence, dIKK-gamma, Filament, surface, MYH17, myosin 1, Actin-Activated ATPase, DmIKK-gamma, dmIKKgamma, IKK[[gamma]], nucleo atomico, alpha-Actin, nuclei, Organ Weight, l(3)s2612, tissue maintenance, Actin Microfilaments, nucleus of CNS, nucleo, noyau, F-Actin, sensory subsystem, dependence, Gallensaeure, ATPase, Actin Filaments, IKK, myosin, Microfilament, nucleus, DmelCG10293, Biliary, Hepatic, Yki, YKI, organa sensuum, Behaviors, Yorkie, alpha Actin, Controlled, Organ, Controlling, COB1, Hippo, Hippo Signaling Pathways, Actomyosin Adenosinetriphosphatase, clone 2.39, fel, Myosin, qkr, l(3)S090417, Cell, bile salts, IKKgamma, count in organism, nervous system nucleus, KH93F, hippo signalling cascade, CG4005, F-actin, Cytoskeleton, SWH pathway, who, Regenerations, Acceptance, PNMHH, MYOSIN, G Actin, Adenosine Triphosphatase, Dmikkgamma, body surface, prophylaxis, nucleus of neuraxis, Who/How, Actomyosin ATPase, AI325207, CG16910, neuraxis nucleus, alpha-Isoactin, Actomyosin, Actin Filament, Pressures, 5beta-bile acids, control, gall, F Actin, qkr[93F], Organ Volume, Actin Cytoskeletons, Actin-ActivatedRegenerations, YAP2, YAP65, COB1, Hippo, Hippo Signaling Pathways, Liver, DmelCG4005, NPIPA, Yap, YAP, NPIP, YY1AP, Yap65, Hippo Signaling, AI325207, Hippo Pathway, temporal, Liver., yap, morpheus, Signaling Pathway, HCCA1, HCCA2, CG4005, Regeneration, Liver Regenerations, Yki, YKI, Yorkie, activation, incidencefalseMorpheus model of spatio-temporal YAP/Hippo pathway activation during liver regenerationMorpheus model of spatio-temporal YAP/Hippo pathway activation during liver regeneration2020-11-272020-11-272020-11-272020-11-2776032090478