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

Research output: Contribution to journalArticlepeer-review

Authors

  • Pedro Sampaio
  • Rita R Ferreira
  • Adán Guerrero
  • Petra Pintado
  • Bárbara Tavares
  • Joana Amaro
  • Susana S Lopes

Colleges, School and Institutes

External organisations

  • CEDOC, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, 1169-056 Lisboa, Portugal.
  • 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.
  • 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.

Bibliographic note

Copyright © 2014 Elsevier Inc. All rights reserved. Author Thomas Johnson writes under Montenegro-Johnson

Details

Original languageEnglish
Pages (from-to)716-28
Number of pages13
JournalDevelopmental Cell
Volume29
Issue number6
Publication statusPublished - 23 Jun 2014