Although the human body is externally symmetric across the left-right axis, there are remarkable left-right asymmetries in the shape, size, and positioning of many internal organs, including the heart, lungs, liver, stomach, and brain. These asymmetries can range from benign to serious, causing a range of conditions that affect multiple organs.
- Mass General Communications
Developmental biologists have long been fascinated by how this asymmetry arises in the first place.
Scientists have long known that left-right asymmetry occurs during early embryonic development, driven by a structure called the left-right organizer, made up of a small cluster of cells. Within the "organizer," motile cilia, hairlike structures on the surface of cells, beat rapidly to create a leftward directional flow of extracellular fluid as the first outward sign of a left-right difference.
And while research has shown that this early flow is critical in the distinction of right from left, just how this flow is sensed and translated into left-right asymmetry has remained unknown.
Now, a new study led by Harvard Medical School researchers at Massachusetts General Hospital answers this question.
The team's findings reveal that cilia - as the creators of flow - also act as sensors for the biomechanical forces exerted by the flow to shape the left-right body plan of the developing embryo.
The findings are published in the journal Science.
"Nearly 25 years of work by numerous groups has shown that cilia and flow in the organizer are absolutely essential for establishing body left-right asymmetry," said Shiaulou Yuan, assistant professor of medicine at HMS, senior author of the study, and an investigator in the Cardiovascular Research Center at Mass General. "But we haven't had the right tools or techniques to definitively study how this all works."
For their work, the researchers used zebrafish as a model for left-right development and employed a novel optical toolkit consisting of custom-built microscopy and machine learning analysis.
