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| The muscles connected to the ears of a human do not develop enough to have the same mobility allowed to many animals. (Photo credit: Wikipedia) |
BY CARL ZIMMER
Some muscles get all
the glory. But deep inside of us, a sheet of muscle does heroic work in
obscurity. The diaphragm delivers oxygen to us a dozen times or more each
minute, a half-billion times during an 80-year life.
“We are completely dependent on the diaphragm,” said
Gabrielle Kardon of the University of Utah.
All mammals have a diaphragm. But no other animal has one.
Before the evolution of a diaphragm, our reptile-like ancestors probably breathed
the way many reptiles do today. They used a jacket of muscles to squeeze the
rib cage.
Once the diaphragm evolved, breathing changed drastically.
Mammals gained a more efficient means to draw in a steady supply of oxygen. The
evolution of a diaphragm may have made it possible for mammals to then evolve a
warm-blooded metabolism. Without a diaphragm, humans might not have been able
to evolve giant – but oxygen-hungry – brains.
Scientist suspect that the diaphragm evolved through a
change in the way mammal embryos develop: Mutations caused certain embryonic
cells to grow into a new muscle. Dr. Kardon and other researchers are trying to
understand that shift and why the muscle sometimes fails to develop, with
catastrophic consequences.
One in every 2,500 babies is born with a hole in its
diaphragm. The baby’s liver, intestines and other abdominal organs can push up
through this opening against the lungs, stunting their growth and restricting
breathing. About a third of babies born with congenital diaphragmatic hernias
die.
Scientists have found that mutations in certain genes can increase
the risk of developing hernias. But they have struggled to figure out exactly
how these genes build the diaphragm. Dr. Kardon and her colleagues developed
new tools to get a closer look. They published the research in Nature Genetics.
The scientists engineered mice so that certain types of
cells would glow inside mouse embryos. Then they tracked the cells as they
multiplied and migrated.
The diaphragm begins as a pair of folds flanking the
esophagus, they found. These folds then expand in two waves. “It’s beautiful,
aesthetically,” said Dr. Kardon. In the first, the cells become connective
tissue across the top of the liver.
In the second wave, cells form a second sheet sandwiched
inside the membrane. “The muscle cells are kind of dumb, and they’re just
following the connective tissue,” said Dr. Kardon.
The researchers then examined GATA4, a gene linked to
diaphragmatic hernias. They engineered mouse embryos so they could shut down GATA4
in certain types of cells at certain points in development. In one trial, the
scientists turned off GATA4 in the muscle cells in the diaphragm. In these
cases, the mice formed diaphragms. When they shut down GATA4 in the connective tissue,
the mice developed hernias. Connective tissue cells must be using GATA4 to lay
down a chemical trail for muscle cells, Dr. Kardon concluded. They can still
lay down the trail if they have one defective copy of the GATA4 gene.
Each time the connective tissue cells divide, there is a
chance that a working copy of GATA4 may mutate, too. If that happens, the
mutant cell and its descendants can’t lay down a trail, resulting in a gap in
the sheet of muscle. As the liver pushes against the diaphragm, the pressure
creates intense stress in the gap, causing the diaphragm to rupture.
John J. Greer, a biologist at the University of Alberta,
said he was skeptical that this scenario could account for most hernias.
He noted that most medical cases of congenital diaphragmatic
hernias occurred in the back left or right corners of the diaphragm. Dr.Kardon
and her colleagues produced many hernias in the middle or front of the
diaphragm of their mouse subjects.
Dr. Kardon countered that a lot of hernias occur in other
parts of the diaphragm, but doctors fail to notice many of them, because the
lungs sit at the back of the diaphragm, hernias there can be dangerous. Hernias
elsewhere can be harmless.
“Because they don’t have serious medical consequences, they
go un-noticed,” she said.
Clifford J. Tabin, a geneticist at Harvard Medical School,
said that the new study offers a molecular explanation for how congenital
diaphragmatic hernias occur. “I think it is a beautiful study and terribly
important,” he said.
Taken from TODAY
Saturday Edition, The New York Times International Weekly, 25 April 2015
