Days 3 to 5 Blastocyst
Cells make their first choice
By the time a three-day-old human embryo enters the uterus, it contains 16
identical cells packed together to form a sphere called a morula. As it moves
into the uterus, the embryo is preparing for a major transformation. During
the next 48 hours, the morula will become a blastocyst — a hollow oval
with about 100 cells divided into two different types. Cells that will form
the placenta make up the outer layer of the blastocyst. Nestled inside is a
small inner cell mass with about 50 cells. These 50 cells will give rise to
the millions of specialized cells, tissues and organs it takes to make a newborn
Scientists refer to cells in the inner cell mass as being pluripotent, meaning
they can become nearly any cell in the human body. But this unlimited potential
lasts for just a few days. If pluripotent cells are removed from the blastocyst
and cultured in the laboratory under the right conditions, they form colonies
of human embryonic stem cells. Otherwise, they are quick to get on with the
business of becoming the specialized cells the embryo will need as it grows
Sue O’Shea, Ph.D., a professor of cell and developmental biology who
directs the Michigan Center for Human Embryonic Stem Cell Research, is trying
to decipher the flood of genetic signals involved in the transformation of
early embryonic cells into cells that are differentiated, or specialized to
perform specific tasks. Working with mouse embryos, mouse embryonic stem cells
and human embryonic stem cell lines that have been approved by the federal
government for use in scientific research, O’Shea and her graduate students
Nicky Slawney and Lisa DeBoer are identifying the genes and growth factors
involved and learning how they work.
O’Shea is especially interested in teasing out the signals required
to transform human embryonic stem cells, and cells in the early embryo, into
neurons — one of the first specialized cells to develop in an embryo.
Week 2 Implantation
At home in the uterine wall
When the human embryo is around six days old, it starts making a nest in the
wall of the mother’s uterus. Cells in the outer layer of the blastocyst
stick to the uterine wall and grow long projections into it — the first
step in developing a placenta with blood vessels linking mother and embryo.
From now on, the embryo will depend on oxygen and nutrients from the mother’s
bloodstream to survive. As the placenta grows and embeds itself within the
uterine wall, the inner cell mass divides to form the amniotic cavity and a
flat disc with two layers of cells that is the embryo.
Once the embryo is embedded in the wall of the uterus, it starts preparing
for a transformation called gastrulation that takes place during the third
week of development. During this process, every cell in the flat disc will
migrate to a new location and morph into one of three new cell types to form
the inner, middle and outer layers of the 21-day-old embryo. This intricate
cellular choreography is regulated by growth factors turned on and off at specific
times and locations in response to signals from the embryo’s genes.
“The embryo uses the same seven growth factor signaling pathways over
and over,” O’Shea says. “But by varying signal strength,
turning cell receptors on or off, or turning growth factors on or off at specific
locations in the embryo, the process allows for a great deal of precision and
Week 3 Gastrulation
Three cell layers and a body plan
During its third week, the human embryo goes through a developmental milestone.
Gastrulation establishes the embryo’s basic body plan and seals the fate
of its cells. Once the process is complete, the embryo will have three distinct
layers with a defined top and bottom, front and back, left and right. At no
other time in its development will the embryo undergo such a radical transformation.
Gastrulation begins with an indentation called the primitive streak, which
forms on top of the flat disc when the embryo is about 15 days old. At the
top of the streak is a small structure called the node that churns out growth
factors signaling cells to break free from their neighbors, multiply and move
toward the streak. Cells in the gastrulating embryo are exquisitely sensitive
to the strength of growth factors from the node. Embryonic cells closest to
the node receive the strongest signal, inducing them to turn on genes that
cause them to become one kind of cell.
Cells on the edge of the embryo receive a weaker signal and this causes them
to express different genes and become a different kind of cell. “Just
being a couple cell diameters away can mean a big difference in gene expression,” O’Shea
Directed by the node, cells move down and through the streak to be reborn
on the other side as either endoderm (the inner layer of the embryo) or mesoderm
(the middle layer). Once the two inner layers of the embryo are formed, the
node sends a different signal to the remaining cells. Instead of going through
the streak, these cells will fan out to form the outer layer of the embryo
called the ectoderm.
Once cells have passed through the primitive streak and gastrulation is complete,
there is no turning back. Each embryonic cell is now destined to follow a specific
developmental pathway. Endoderm cells will go on to form the liver, pancreas
and gastrointestinal tract. Cells in the mesoderm are fated to develop into
the heart and blood vessels, bone, muscle and kidneys. The ectoderm will become
the central and peripheral nervous systems, sensory organs, skin and hair.
Because the blueprint for all the body’s organs is established during
gastrulation, it’s the beginning of a time when exposure to alcohol,
drugs, viruses and toxic chemicals can have a catastrophic effect on the embryo.
From the third week to the eighth week while organs are still forming, the
embryo will remain vulnerable to damage. Even if it’s not lethal, the
result can be a lifetime of disability for a child born with fetal alcohol
syndrome or spina bifida.
Knowing more about what happens to a human embryo during its perilous journey
from fertilization to gastrulation could help researchers learn what causes
birth defects and perhaps even find ways to prevent or correct them.
Research to understand how embryos develop could benefit the health of adults,
as well. Scientists are only starting to understand how mistakes during embryogenesis
can have life-long consequences in the form of diseases and disorders like
cancer, congenital heart defects, and Down syndrome that begin when something
goes wrong during the embryo’s first 21 days.
Beyond the First 21 Days: The Center for Organogenesis