Fluid extraction from the left-right organizer uncovers mechanical properties needed for symmetry breaking.

Autor:	Sampaio P; CEDOC, Chronic Diseases Research Centre, NOVA Medical School. Faculdade de8 Ciências Médicas, Universidade Nova de Lisboa, Lisboa, Portugal., Pestana S; CEDOC, Chronic Diseases Research Centre, NOVA Medical School. Faculdade de8 Ciências Médicas, Universidade Nova de Lisboa, Lisboa, Portugal., Bota C; CEDOC, Chronic Diseases Research Centre, NOVA Medical School. Faculdade de8 Ciências Médicas, Universidade Nova de Lisboa, Lisboa, Portugal., Guerrero A; Laboratorio Nacional de Microscopía Avanzada. Departamento de Genética del Desarrollo y Fisiología Molecular. Instituto de Biotecnología. Universidad Nacional Autónoma de México (UNAM), Cuernavaca, Mexico., Telley IA; Instituto Gulbenkian de Ciência, Fundação Calouste Gulbenkian, Oeiras, Portugal., Smith D; School of Mathematics, University of Birmingham, Birmingham, United Kingdom.; Institute for Metabolism and Systems Research, University of Birmingham, Birmingham, United Kingdom., Lopes SS; CEDOC, Chronic Diseases Research Centre, NOVA Medical School. Faculdade de8 Ciências Médicas, Universidade Nova de Lisboa, Lisboa, Portugal.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2023 Jul 21; Vol. 12. Date of Electronic Publication: 2023 Jul 21.
DOI:	10.7554/eLife.83861
Abstrakt:	Humans and other vertebrates define body axis left-right asymmetry in the early stages of embryo development. The mechanism behind left-right establishment is not fully understood. Symmetry breaking occurs in a dedicated organ called the left-right organizer (LRO) and involves motile cilia generating fluid-flow therein. However, it has been a matter of debate whether the process of symmetry breaking relies on a chemosensory or a mechanosensory mechanism (Shinohara et al., 2012). Novel tailored manipulations for LRO fluid extraction in living zebrafish embryos allowed us to pinpoint a physiological developmental period for breaking left-right symmetry during development. The shortest critical time-window was narrowed to one hour and characterized by a mild counterclockwise flow. The experimental challenge consisted in emptying the LRO of its fluid, abrogating simultaneously flow force and chemical determinants. Our findings revealed an unprecedented recovery capacity of the embryo to re-fil and re-circulate new LRO fluid. The embryos that later developed laterality problems were found to be those that had lower anterior angular velocity and thus less anterior-posterior heterogeneity. Next, aiming to test the presence of any secreted determinant, we replaced the extracted LRO fluid by a physiological buffer. Despite some transitory flow homogenization, laterality defects were absent unless viscosity was altered, demonstrating that symmetry breaking does not depend on the nature of the fluid content but is rather sensitive to fluid mechanics. Altogether, we conclude that the zebrafish LRO is more sensitive to fluid dynamics for symmetry breaking. Competing Interests: PS, SP, CB, AG, IT, DS, SL No competing interests declared (© 2023, Sampaio, Pestana et al.)
Databáze:	MEDLINE
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