Modeling Genetic Disruptions in Heart Development

During heart development, cells move and interact to establish their positions—an essential process where the right pairings determine whether the heart functions properly.

A recent study in the Biophysical Journal explores this intricate “matchmaking” among heart cells. Researchers simulated these cellular movements and predicted how genetic variations might impact heart formation in fruit flies.

In both humans and fruit flies, heart tissue originates from two distinct regions of the embryo, initially far apart. As development progresses, these cells migrate toward each other, eventually forming a tube-like structure that will develop into the heart. Accurate alignment and pairing are crucial for proper heart formation.

“As the cells come together, they jiggle and adjust, yet they always end up pairing with a heart cell of the same type.”

Timothy Saunders, Study Lead Author, University of Warwick

This observation led the team to investigate how cells recognize and pair with the correct match.

Heart cells use tentacle-like extensions called filopodia to explore and latch onto potential partners. Previous research by Saunders showed that proteins create waves that separate mismatched cells, giving them another chance to find the right pairing.

“It’s basically like speed dating. Cells have only a few moments to determine if they’re a good match, with molecular ‘friends’ pulling them apart if they’re not compatible.”

Timothy Saunders, Study Lead Author, University of Warwick

The study found that heart cells seek stability, similar to a rolling ball coming to rest—a concept known as energy equilibrium in physics. This balance is achieved through adhesive energy (cell-to-cell stickiness) and elasticity (the ability to adapt to strain).

Using these principles, the researchers developed a computational model to predict how cells self-organize. They then tested the model on mutated fruit fly hearts, where misalignments sometimes left too few or too many cells in certain areas.

“We could input these imperfections into the model and run it.”

Timothy Saunders, Study Lead Author, University of Warwick

The model’s predictions closely matched real-world observations in developing embryos.

The researchers highlight that this cell-matching mechanism extends beyond heart formation. Similar processes are crucial in neuronal connections, wound healing, and facial development, where disruptions can lead to conditions like cleft lip.

“Essentially, we are putting numbers to biological processes to explain what we observe.”

Timothy Saunders, Study Lead Author, University of Warwick

By quantifying these biological interactions, the study offers new insights into developmental biology and potential applications for medical research and regenerative medicine.