Chiral cilia orientation in the left-right organizer

Abstract

Chirality is a property of asymmetry between an object and its mirror image. Most biomolecules and cells are intrinsically chiral. Whether cellular chirality can be transferred to asymmetry at the tissue scale remains an unresolved issue. This question is particularly relevant in the left-right organizer (LRO), where cilia motility and chiral flow are thought to be the main drivers of left-right axis symmetry breaking. Here, we built a quantitative approach based on live imaging to set apart the contributions of various pathways to the spatial orientation of cilia in the Kupffers vesicle (KV, zebrafish LRO). We found that cilia populating the zebrafish LRO display an asymmetric orientation between the right and left side of the LRO. Cilia orientations, therefore, give the KV cells a sense of chirality which is different from the chirality of cilia rotation. Surprisingly, we found this asymmetry does not depend on the left-right signalling pathway or flow. Furthermore, we show the establishment of the chirality is dynamic and depends on planar cell polarity. Together, this work identifies a different type of asymmetry in the LRO and sheds light on the complexity of chirality genesis in developing tissues.