For the first time, remarkable time-lapse imagery has illustrated the moment when a heart starts to develop.
This visual documentation reveals that cardiac cells within a mouse embryo begin to intrinsically arrange themselves into a heart-like configuration during the early stages of development. Researchers believe this methodology could shed light on congenital heart defects, conditions affecting nearly one out of every 100 newborns.
“This is unprecedented; we’ve managed to closely observe heart cells for an extended period during mammalian development,” stated Dr. Kenzo Ivanovitch, the lead researcher at University College London’s Great Ormond Street Institute of Child Health. “We first needed to reliably culture the embryos in vitro for extended durations, spanning from several hours to multiple days, and the results were completely unforeseen.”
The embryonic development footage was obtained through a technique known as advanced light-sheet microscopy, enabling scientists to monitor the embryos during a critical development phase called gastrulation. This phase is characterized by the emergence of distinct cell lineages and the formation of the foundational body axes.
Shortly thereafter, cardiac muscle cells arrange into a significant tubular structure, which will later divide into sections that eventually become the heart’s walls and chambers. In infants with heart defects, a gap can emerge during this developmental stage.
By employing fluorescent markers, the research team tagged the heart muscle cells, known as cardiomyocytes, which made them emit distinct colors. Images were recorded every two minutes over a 40-hour period, capturing the movement, division, and early formation of the organ, thereby allowing researchers to pinpoint when and where the initial heart cells appeared in the embryo.
The researchers determined that during the early phase of gastrulation (about six days into the development of a mouse embryo), cells destined to form the heart appeared rapidly and exhibited highly organized behaviors. Instead of moving in a haphazard manner, these cells began to follow specific paths, contributing to either the ventricles (the heart’s pumping chambers) or the atria (the receiving chambers for blood returning from the body and lungs).
“Our results indicate that the determination of cardiac fate and the directed movement of cells may be regulated substantially earlier in development than previously thought,” Ivanovitch remarked. “This significantly reshapes our comprehension of heart development by illustrating that what might seem like disorganized cell migration is actually guided by underlying patterns that facilitate accurate heart formation.”
The team believes these insights could enhance the understanding and treatment of congenital heart defects and expedite advancements in the cultivation of heart tissue in the laboratory for applications in regenerative medicine.
These findings were published in The EMBO Journal.
