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PMID:21285373

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Citation

Blitzer, AL, Panagis, L, Gusella, GL, Danias, J, Mlodzik, M and Iomini, C (2011) Primary cilia dynamics instruct tissue patterning and repair of corneal endothelium. Proc. Natl. Acad. Sci. U.S.A. 108:2819-24

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.

Links

PubMed PMC3041123 Online version:10.1073/pnas.1016702108

Keywords

Animals; Cilia/physiology; Corneal Endothelial Cell Loss/physiopathology; Endothelium, Corneal/embryology; Endothelium, Corneal/injuries; Endothelium, Corneal/ultrastructure; Gene Knockdown Techniques; In Situ Nick-End Labeling; Mice; Mice, Inbred C57BL; Microscopy, Electron, Scanning; Microscopy, Fluorescence; Morphogenesis; RNA Interference; Tumor Suppressor Proteins/genetics

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:ZO1

located_in

GO:0005923: bicellular tight junction

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:IFT88

acts_upstream_of_or_within

GO:0001886: endothelial cell morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2157527

P

  • occurs_in:(EMAPA:35935)
  • results_in_morphogenesis_of:(CL:0000132)

Seeded From UniProt

complete

MOUSE:IFT88

acts_upstream_of_or_within

GO:1905515: non-motile cilium assembly

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2157527

P

  • occurs_in:(CL:0000132)
  • occurs_in:(EMAPA:35935)

Seeded From UniProt

complete

MOUSE:IFT88

acts_upstream_of_or_within

GO:1905515: non-motile cilium assembly

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2157527

P

Seeded From UniProt

complete

MOUSE:IFT88

acts_upstream_of_or_within

GO:0001886: endothelial cell morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2157527

P

Seeded From UniProt

complete


See also

References

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