PUBLICATION

Left-Right Organizer Flow Dynamics: How Much Cilia Activity Reliably Yields Laterality?

Authors
Sampaio, P., Ferreira, R.R., Guerrero, A., Pintado, P., Tavares, B., Amaro, J., Smith, A.A., Montenegro-Johnson, T., Smith, D.J., Lopes, S.S.
ID
ZDB-PUB-140617-4
Date
2014
Source
Developmental Cell   29(6): 716-28 (Journal)
Registered Authors
Lopes, Susana
Keywords
none
MeSH Terms
  • Animals
  • Cilia/physiology*
  • Computer Simulation
  • Dyneins/metabolism*
  • Embryo, Nonmammalian/cytology
  • Embryo, Nonmammalian/metabolism*
  • Fluorescent Antibody Technique
  • Functional Laterality*
  • Gastrointestinal Tract/cytology
  • Gastrointestinal Tract/metabolism
  • Heart/physiology
  • In Situ Hybridization
  • Models, Theoretical
  • Zebrafish/embryology
  • Zebrafish/metabolism*
  • Zebrafish Proteins/metabolism*
PubMed
24930722 Full text @ Dev. Cell
Abstract
Internal organs are asymmetrically positioned inside the body. Embryonic motile cilia play an essential role in this process by generating a directional fluid flow inside the vertebrate left-right organizer. Detailed characterization of how fluid flow dynamics modulates laterality is lacking. We used zebrafish genetics to experimentally generate a range of flow dynamics. By following the development of each embryo, we show that fluid flow in the left-right organizer is asymmetric and provides a good predictor of organ laterality. This was tested in mosaic organizers composed of motile and immotile cilia generated by dnah7 knockdowns. In parallel, we used simulations of fluid dynamics to analyze our experimental data. These revealed that fluid flow generated by 30 or more cilia predicts 90% situs solitus, similar to experimental observations. We conclude that cilia number, dorsal anterior motile cilia clustering, and left flow are critical to situs solitus via robust asymmetric charon expression.
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