The growth of the
zebrafish heart from embryo to adult is tracked using colored cardiac muscle
clones, each containing many cellular progeny of a single cardiac muscle cell.
Here, a large clone of green cardiac muscle cells (top) expands over the
surface of many smaller clones in a growing heart. Credit: Vikas Gupta, Duke
University Medical Center
Just
a handful of cells in the embryo are all that's needed to form the outer layer
of pumping heart muscle in an adult zebrafish.
Researchers at Duke University Medical Center used
zebrafish embryos and careful employment of a new technique that allows for up
to 90 color labels on different cells to track individual cells and cell lines
as the heart formed.
The scientists were surprised by how few cells went
into making a critical organ structure and they suspect that other organs may
form in a similar fashion, said Kenneth Poss, Ph.D., professor in the Duke
Department of Cell Biology and Howard Hughes Medical Institute.
The study appears online in Nature on
April 25.
"The most surprising aspect of this work is
that a very small number of cardiomyocytes (heart muscle cells)
in the growing animal can give rise to the thousands of cardiomyocytes that
form the wall of the cardiac ventricle," said Vikas Gupta, lead author,
who is in the Duke Medical Scientist Training Program for M.D. and Ph.D.
degrees.
Gupta found that about eight single cells
contributed to forming the major type of heart muscle in the
wall of the zebrafish heart -- and just one or two cells could create anywhere
from 30 to 70 percent of the entire ventricular surface.
"Clonal dominance like this is a property of
some types of stem cells, and it's a new concept in how to form an organ during
development," Poss said.
Another surprise was the way the patches of cloned
cells formed muscle.
"It was completely unexpected," Gupta
said. "I thought the wall would simply thicken in place, but instead there
was a network of cells that enveloped the ventricle in a wave. It was as if a
cell at your shoulder grew a thin layer of new cells down your arm
surface."
Gupta said this opens an area for investigation to
see whether or not a process like this repeats in the hearts of mammals, and
perhaps in other internal
organs.
Poss said the cell clones appear to have the ability
to cover as much of the ventricular surface as possible before other cells
start appearing and growing at the surface.
"Our suspicion is that the muscle cells that
initiate large clones are not much different from other muscle cells – they
just get to the surface of the heart first," Poss said.
They used the analogy of a sperm getting to the egg
first, among all the millions of possible sperm cells.
Poss said the manner in which these muscle cells
envelope the heart could lead to new therapies.
"Researchers may be able to channel this
developmental process to help damaged hearts or failing hearts to grow muscle
that will reinforce the ventricular walls," he said. "Someone who's
had a heart attack would want this ability to generate new muscle to cover a
scar naturally, and it's attractive to think that the help might come from a
small number of muscle
cells within a population."
The color-label technique was originally developed
by other biologists and was critical to allow the researchers to track heart
cell populations.
"You can label individual cells very early in
an embryo with a permanent color and those cells and their progeny
will keep that color," Poss said. "You can learn what an individual
cardiomyocyte did, and its neighbor, and that cell's neighbor and so on, until
you've covered much of the whole ventricle of the
developing zebrafish."
Poss said it makes sense that this growth process
works by a gradual layering process, especially for the heart. "It's
speculative, but for the heart to maintain circulation in a relatively slowly
growing animal, a process like this to build the heart might be a way of
gradually increasing its circulatory strength to keep up."
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