title: Cilia-driven fluid flow in the zebrafish pronephros, brain and Kupffer's vesicle is required for normal organogenesis.
abstract: Cilia, as motile and sensory organelles, have been implicated in normal development, as well as diseases including cystic kidney disease, hydrocephalus and situs inversus. In kidney epithelia, cilia are proposed to be non-motile sensory organelles, while in the mouse node, two cilia populations, motile and non-motile have been proposed to regulate situs. We show that cilia in the zebrafish larval kidney, the spinal cord and Kupffer's vesicle are motile, suggesting that fluid flow is a common feature of each of these organs. Disruption of cilia structure or motility resulted in pronephric cyst formation, hydrocephalus and left-right asymmetry defects. The data show that loss of fluid flow leads to fluid accumulation, which can account for organ distension pathologies in the kidney and brain. In Kupffer's vesicle, loss of flow is associated with loss of left-right patterning, indicating that the 'nodal flow' mechanism of generating situs is conserved in non-mammalian vertebrates.
authors.affiliation: Renal Unit, Massachusetts General Hospital, 149 13th Street, Charlestown, MA 02129, USA.
authors.forename: Albrecht G
authors.initials: AG
authors.lastname: Kramer-Zucker
authors.forename: Felix
authors.initials: F
authors.lastname: Olale
authors.forename: Courtney J
authors.initials: CJ
authors.lastname: Haycraft
authors.forename: Bradley K
authors.initials: BK
authors.lastname: Yoder
authors.forename: Alexander F
authors.initials: AF
authors.lastname: Schier
authors.forename: Iain A
authors.initials: IA
authors.lastname: Drummond
mesh_terms: D000818:Animals; D001483:Base Sequence; D001826:Body Fluids / Q000502:physiology*; D019521:Body Patterning / Q000502:physiology; D002490:Central Nervous System / Q000196:embryology*; D002923:Cilia / Q000502:physiology*; D003001:Cloning, Molecular; D017931:DNA Primers; D004398:Dyneins / Q000235:genetics; D004625:Embryo, Nonmammalian / Q000196:embryology / Q000648:ultrastructure; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007668:Kidney / Q000196:embryology*; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D018715:Microscopy, Video; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics; D009841:Oligonucleotides; D020897:Organizers, Embryonic / Q000196:embryology*; D038081:Organogenesis / Q000502:physiology*; D017422:Sequence Analysis, DNA; D015027:Zebrafish / Q000196:embryology*
chemical_list: D017931:DNA Primers; D009419:Nerve Tissue Proteins; D009841:Oligonucleotides; D004398:Dyneins