title: Left-right organizer flow dynamics: how much cilia activity reliably yields laterality?
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.
authors.affiliation: CEDOC, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, 1169-056 Lisboa, Portugal.
authors.forename: Pedro
authors.initials: P
authors.lastname: Sampaio
authors.affiliation: CEDOC, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, 1169-056 Lisboa, Portugal.
authors.forename: Rita R
authors.initials: RR
authors.lastname: Ferreira
authors.affiliation: 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.
authors.forename: Adán
authors.initials: A
authors.lastname: Guerrero
authors.affiliation: CEDOC, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, 1169-056 Lisboa, Portugal.
authors.forename: Petra
authors.initials: P
authors.lastname: Pintado
authors.affiliation: CEDOC, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, 1169-056 Lisboa, Portugal.
authors.forename: Bárbara
authors.initials: B
authors.lastname: Tavares
authors.affiliation: CEDOC, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, 1169-056 Lisboa, Portugal.
authors.forename: Joana
authors.initials: J
authors.lastname: Amaro
authors.affiliation: 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.
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Smith
authors.affiliation: 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.
authors.forename: Thomas
authors.initials: T
authors.lastname: Montenegro-Johnson
authors.affiliation: 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.
authors.forename: David J
authors.initials: DJ
authors.lastname: Smith
authors.affiliation: CEDOC, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, 1169-056 Lisboa, Portugal. Electronic address: susana.lopes@fcm.unl.pt.
authors.forename: Susana S
authors.initials: SS
authors.lastname: Lopes
mesh_terms: D000818:Animals; D002923:Cilia / Q000502:physiology*; D003198:Computer Simulation; D004398:Dyneins / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D007839:Functional Laterality; D041981:Gastrointestinal Tract / Q000166:cytology / Q000378:metabolism; D006321:Heart / Q000502:physiology; D017403:In Situ Hybridization; D008962:Models, Theoretical; D015027:Zebrafish / Q000196:embryology / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000378:metabolism*
chemical_list: D029961:Zebrafish Proteins; D004398:Dyneins