title: Dynamics of cilia length in left-right development.
abstract: Reduction in the length of motile cilia in the zebrafish left-right organizer (LRO), also known as Kupffer's vesicle, has a large impact on left-right development. Here we demonstrate through genetic overexpression in zebrafish embryos and mathematical modelling that the impact of increased motile cilia length in embryonic LRO fluid flow is milder than that of short cilia. Through Arl13b overexpression, which increases cilia length without impacting cilia beat frequency, we show that the increase in cilium length is associated with a decrease in beat amplitude, resulting in similar flow strengths for Arl13b overexpression and wild-type (WT) embryos, which were not predicted by current theory. Longer cilia exhibit pronounced helical beat patterns and, consequently, lower beat amplitudes relative to WT, a result of an elastohydrodynamic shape transition. For long helical cilia, fluid dynamics modelling predicts a mild (approx. 12%) reduction in the torque exerted on the fluid relative to the WT, resulting in a proportional reduction in flow generation. This mild reduction is corroborated by experiments, providing a mechanism for the mild impact on organsitus.
authors.affiliation: NOVA Medical School Faculdade de Ciências Médicas, Chronic Diseases Research Centre, CEDOC , Universidade Nova de Lisboa , Campo Mártires da Pátria, 130, 1169-056 Lisboa , Portugal.
authors.forename: P
authors.identifier: 0000-0003-3635-6220
authors.initials: P
authors.lastname: Pintado
authors.affiliation: NOVA Medical School Faculdade de Ciências Médicas, Chronic Diseases Research Centre, CEDOC , Universidade Nova de Lisboa , Campo Mártires da Pátria, 130, 1169-056 Lisboa , Portugal.
authors.forename: P
authors.identifier: 0000-0002-6197-1068
authors.initials: P
authors.lastname: Sampaio
authors.affiliation: NOVA Medical School Faculdade de Ciências Médicas, Chronic Diseases Research Centre, CEDOC , Universidade Nova de Lisboa , Campo Mártires da Pátria, 130, 1169-056 Lisboa , Portugal.
authors.forename: B
authors.identifier: 0000-0002-4048-8915
authors.initials: B
authors.lastname: Tavares
authors.affiliation: School of Mathematics , University of Birmingham , Birmingham , UK.
authors.forename: T D
authors.identifier: 0000-0002-9370-7720
authors.initials: TD
authors.lastname: Montenegro-Johnson
authors.affiliation: School of Mathematics, University of Birmingham, Birmingham, UK; Institute for Metabolism and Systems Research, University of Birmingham, Birmingham, UK; Centre for Human Reproductive Science, Birmingham Women's NHS Foundation Trust, Birmingham, UK.
authors.forename: D J
authors.identifier: 0000-0002-3427-0936
authors.initials: DJ
authors.lastname: Smith
authors.affiliation: NOVA Medical School Faculdade de Ciências Médicas, Chronic Diseases Research Centre, CEDOC , Universidade Nova de Lisboa , Campo Mártires da Pátria, 130, 1169-056 Lisboa , Portugal.
authors.forename: S S
authors.identifier: 0000-0002-6733-6356
authors.initials: SS
authors.lastname: Lopes
keywords: cilia length; flow dynamics; left–right development