title: Primary cilia dynamics instruct tissue patterning and repair of corneal endothelium.
abstract: Primary cilia are required for several signaling pathways, but their function in cellular morphogenesis is poorly understood. Here we show that emergence of an hexagonal cellular pattern during development of the corneal endothelium (CE), a monolayer of neural crest-derived cells that maintains corneal transparency, depends on a precise temporal control of assembly of primary cilia that subsequently disassemble in adult corneal endothelial cells (CECs). However, cilia reassembly occurs rapidly in response to an in vivo mechanical injury and precedes basal body polarization and cellular elongation in mature CECs neighboring the wound. In contrast, CE from hypomorphic IFT88 mutants (Tg737(orpk)) or following in vivo lentiviral-mediated IFT88 knockdown display dysfunctional cilia and show disorganized patterning, mislocalization of junctional markers, and accumulation of cytoplasmic acetylated tubulin. Our results indicate an active role of cilia in orchestrating coordinated morphogenesis of CECs during development and repair and define the murine CE as a powerful in vivo system to study ciliary-based cellular dynamics.
authors.affiliation: Department of Developmental and Regenerative Biology, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Blitzer
authors.forename: Lampros
authors.initials: L
authors.lastname: Panagis
authors.forename: G Luca
authors.initials: GL
authors.lastname: Gusella
authors.forename: John
authors.initials: J
authors.lastname: Danias
authors.forename: Marek
authors.initials: M
authors.lastname: Mlodzik
authors.forename: Carlo
authors.initials: C
authors.lastname: Iomini
mesh_terms: D000818:Animals; D002923:Cilia / Q000502:physiology*; D055954:Corneal Endothelial Cell Loss / Q000503:physiopathology*; D004728:Endothelium, Corneal / Q000196:embryology* / Q000293:injuries* / Q000648:ultrastructure; D055785:Gene Knockdown Techniques; D020287:In Situ Nick-End Labeling; D051379:Mice; D008810:Mice, Inbred C57BL; D008855:Microscopy, Electron, Scanning; D008856:Microscopy, Fluorescence; D009024:Morphogenesis; D034622:RNA Interference; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: C490898:Tg737Rpw protein, mouse; D025521:Tumor Suppressor Proteins