title: Intraciliary calcium oscillations initiate vertebrate left-right asymmetry.
abstract: BACKGROUND
  Bilateral symmetry during vertebrate development is broken at the left-right organizer (LRO) by ciliary motility and the resultant directional flow of extracellular fluid. However, how ciliary motility is perceived and transduced into asymmetrical intracellular signaling at the LRO remains controversial. Previous work has indicated that sensory cilia and polycystin-2 (Pkd2), a cation channel, are required for sensing ciliary motility, yet their function and the molecular mechanism linking both to left-right signaling cascades are unknown.
  
  
  RESULTS
  Here we report novel intraciliary calcium oscillations (ICOs) at the LRO that connect ciliary sensation of ciliary motility to downstream left-right signaling. Utilizing cilia-targeted genetically encoded calcium indicators in live zebrafish embryos, we show that ICOs depend on Pkd2 and are left-biased at the LRO in response to ciliary motility. Asymmetric ICOs occur with onset of LRO ciliary motility, thus representing the earliest known LR asymmetric molecular signal. Suppression of ICOs using a cilia-targeted calcium sink reveals that they are essential for LR development.
  
  
  CONCLUSIONS
  These findings demonstrate that intraciliary calcium initiates LR development and identify cilia as a functional ion signaling compartment connecting ciliary motility and flow to molecular LR signaling.
authors: Department of Pediatrics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.
authors: Shiaulou
authors: S
authors: Yuan
authors: Department of Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.
authors: Lu
authors: L
authors: Zhao
authors: Department of Pediatrics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA; Department of Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA. Electronic address: martina.brueckner@yale.edu.
authors: Martina
authors: M
authors: Brueckner
authors: Department of Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA. Electronic address: zhaoxia.sun@yale.edu.
authors: Zhaoxia
authors: Z
authors: Sun
mesh_terms: D020727:ADP-Ribosylation Factors / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D019521:Body Patterning / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology*; D002923:Cilia / Q000378:metabolism*; D045604:Extracellular Fluid / Q000378:metabolism; D059446:Heterotaxy Syndrome / Q000196:embryology*; D006652:Histological Techniques; D006801:Humans; D008954:Models, Biological; D055456:Nodal Signaling Ligands / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D050396:TRPP Cation Channels / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000378:metabolism
chemical_list: D020727:ADP-Ribosylation Factors; D055456:Nodal Signaling Ligands; D050396:TRPP Cation Channels; D029961:Zebrafish Proteins; C545718:Arl13b protein, zebrafish