Immotile cilia sense the direction of extracellular fluid during development to break left-right symmetry

Tiny, immobile cilia sense the direction of extracellular fluid during development to break left-right symmetry during early embryogenesis, researchers report in two independent studies that investigate this mechanism in mice embryos and zebrafish, respectively. Although many vertebrate bodies look symmetrical on the outside, there are numerous left-right asymmetries in the form and organization of internal organs.

These asymmetrical differences are established during early embryogenesis by a small cluster of cells called the left-right organizer (LRO). At a specific point during embryogenesis, motile cilia within this cluster move in unison to create a leftward directional flow of extracellular fluid, which is the first sign of the breaking of bilateral symmetry during early development. However, how this leftward fluid flow is sensed and translated into a signal that triggers left-right asymmetrical development programs remain unknown.

In two independent studies, Takanobu Katoh and colleagues, and Lydia Djenoune and colleagues, respectively, show that immotile cilia in the LRO act as mechanosensors that convert the biomechanical forces of flowing fluid into calcium signals that instruct left-right asymmetry. In mouse embryos, Katoh et al. found that immotile cilia in the LRO undergo deformation along the dorsoventral axis in response to the force the extracellular flow. This, in turn, creates a calcium signal that communicates the direction of the flow. Separately, and working in zebrafish, Dejenoune et al. discovered a similar process in shaping cardiac left-right asymmetry. According to the findings, when the normal flow was stopped, mechanical manipulation of the cilia could rescue and even reverse left-right patterning of the heart. Combined, the findings suggest that this mechanism is evolutionarily conserved and plays a crucial role in breaking bilateral symmetry during development.

Journal reference:

Katoh, T.A., et al. (2023) Immotile cilia mechanically sense the direction of fluid flow for left-right determination. Science.


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