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Dev Cell. 2014 Jun 23;29(6):716-28. doi: 10.1016/j.devcel.2014.04.030. Epub 2014 Jun 12.

Left-right organizer flow dynamics: how much cilia activity reliably yields laterality?

Author information

1
CEDOC, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, 1169-056 Lisboa, Portugal.
2
Instituto Gulbenkian de Ciência, Rua da Quinta Grande 6, 2780-156 Oeiras, Portugal; Laboratorio Nacional de Microscopía Avanzada, Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), Cuernavaca, Morelos 62250, México.
3
School of Mathematics, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK; Centre for Human Reproductive Science, Birmingham Women's NHS Foundation Trust, Edgbaston, Birmingham B15 2TG, UK.
4
CEDOC, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, 1169-056 Lisboa, Portugal. Electronic address: susana.lopes@fcm.unl.pt.

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.

PMID:
24930722
DOI:
10.1016/j.devcel.2014.04.030
[Indexed for MEDLINE]
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