Abstract
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. Although it is known that the symmetry break occurs in a dedicated organ called the left-right organizer (LRO) and involves motile cilia generating fluid flow therein, it has been a matter of debate whether the process of symmetry breaking relies on a chemosensory or a mechanosensory mechanism. Novel tailored manipulations for LRO fluid extraction in living zebrafish embryos allowed us to pinpoint a decisive developmental period for breaking left-right symmetry during development. This critical time-window was narrowed to one hour and is characterized by a mild counterclockwise flow. The experimental challenge in our approach consisted of emptying the LRO of any potential fluid, abrogating simultaneously flow force and chemical determinants. Our findings revealed an unprecedented recovery capacity of the embryo to re-inflate and re-circulate the fluid inside the LRO exposing unknown properties of this transient organ. Live extraction and replacement of LRO fluid while changing dilution or viscosity demonstrated that early left-right patterning depends on fluid flow mechanics rather than on the nature of the fluid content. Our results advocate for a mechanosensory mechanism ruling left-right early development.
Teaser Zebrafish uses mechanosensation during one-hour time-window to initiate left-right development
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
↵* Co-first-authors