title: Regulation by a TGFβ-ROCK-actomyosin axis secures a non-linear lumen expansion that is essential for tubulogenesis.
abstract: Regulation of lumen growth is crucial to ensure the correct morphology, dimensions and function of a tubular structure. How this is controlled is still poorly understood. During Ciona intestinalis notochord tubulogenesis, single extracellular lumen pockets grow between pairs of cells and eventually fuse into a continuous tube. Here, we show that lumen growth exhibits a lag phase, during which the luminal membranes continue to grow but the expansion of the apical/lateral junction pauses for ∼30 min. Inhibition of non-muscle myosin II activity abolishes this lag phase and accelerates expansion of the junction, resulting in the formation of narrower lumen pockets partially fusing into a tube of reduced size. Disruption of actin dynamics, conversely, causes a reversal of apical/lateral junction expansion, leading to a dramatic conversion of extracellular lumen pockets to intracellular vacuoles and a tubulogenesis arrest. The onset of the lag phase is correlated with a de novo accumulation of actin that forms a contractile ring at the apical/lateral junctions. This actin ring actively restricts the opening of the lumen in the transverse plane, allowing sufficient time for lumen growth via an osmotic process along the longitudinal dimension. The dynamics of lumen formation is controlled by the TGFβ pathway and ROCK activity. Our findings reveal a TGFβ-ROCK-actomyosin contractility axis that coordinates lumen growth, which is powered by the dynamics of luminal osmolarity. The regulatory system may function like a sensor/checkpoint that responds to the change of luminal pressure and fine-tunes actomyosin contractility to effect proper tubulogenesis.
authors.affiliation: Sars International Centre for Marine Molecular Biology, University of Bergen, Thormøhlensgt. 55, Bergen N-5008, Norway.
authors.forename: Elsa
authors.initials: E
authors.lastname: Denker
authors.affiliation: Sars International Centre for Marine Molecular Biology, University of Bergen, Thormøhlensgt. 55, Bergen N-5008, Norway.
authors.forename: Ivonne M
authors.initials: IM
authors.lastname: Sehring
authors.affiliation: Sars International Centre for Marine Molecular Biology, University of Bergen, Thormøhlensgt. 55, Bergen N-5008, Norway College of Marine Life Sciences, Ocean University of China, 5 Yushan Road, Qingdao 266003, China Institute of Evolution and Marine Biodiversity, Ocean University of China, 5 Yushan Road, Qingdao 266003, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Dong
authors.affiliation: Sars International Centre for Marine Molecular Biology, University of Bergen, Thormøhlensgt. 55, Bergen N-5008, Norway.
authors.forename: Julien
authors.initials: J
authors.lastname: Audisso
authors.affiliation: Sars International Centre for Marine Molecular Biology, University of Bergen, Thormøhlensgt. 55, Bergen N-5008, Norway.
authors.forename: Birthe
authors.initials: B
authors.lastname: Mathiesen
authors.affiliation: Sars International Centre for Marine Molecular Biology, University of Bergen, Thormøhlensgt. 55, Bergen N-5008, Norway di.jiang@sars.uib.no.
authors.forename: Di
authors.initials: D
authors.lastname: Jiang
mesh_terms: D000205:Actomyosin / Q000378:metabolism*; D000818:Animals; D002938:Ciona intestinalis / Q000196:embryology*; D018274:Electroporation; D007150:Immunohistochemistry; D007365:Intercellular Junctions / Q000502:physiology; D018613:Microscopy, Confocal; D009024:Morphogenesis / Q000502:physiology*; D009672:Notochord / Q000196:embryology*; D010957:Plasmids / Q000235:genetics; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D054460:rho-Associated Kinases / Q000378:metabolism*
chemical_list: D016212:Transforming Growth Factor beta; D000205:Actomyosin; D054460:rho-Associated Kinases
keywords: Actomyosin; Ciona; Lumen formation; Notochord; ROCK; TGFβ; Tubulogenesis