Essential Cell Biology 5th edition

640 CHAPTER 18 The Cell-Division Cycle
(A)
(B)
1 mm
Figure 18−36 Apoptosis in the
developing mouse paw sculpts the digits.
(A) The paw in this mouse embryo has been
stained with a dye that specifically labels
cells that have undergone apoptosis. The
apoptotic cells appear as bright green dots
between the developing digits. (B) This cell
death eliminates the tissue between the
developing digits, as seen in the paw shown
one day later. Here, few, if any, apoptotic
ECB5 e18.35/18.35
cells can be seen—demonstrating how
quickly apoptotic cells can be cleared from a
tissue. (From W. Wood et al., Development
127:5245–5252, 2000. With permission from
The Company of Biologists Ltd.)
Apoptosis Helps Regulate Animal Cell Numbers
The cells of a multicellular organism are members of a highly organized
community. The number of cells in this community is tightly regulated—
not simply by controlling the rate of cell division, but also by controlling
the rate of cell death. If cells are no longer needed, they can remove
themselves by activating an intracellular suicide program—a process
called programmed cell death. In animals, the most common form of
programmed cell death is called apoptosis (from a Greek word meaning
“falling off,” as leaves fall from a tree).
The amount of apoptosis that occurs in both developing and adult animal
tissues can be astonishing. In the developing vertebrate nervous system,
for example, more than half of some types of nerve cells normally die
soon after they are formed. In a healthy adult human, billions of cells in
the bone marrow and intestine perish every hour. It seems remarkably
wasteful for so many cells to die, especially as the vast majority are perfectly
healthy at the time they kill themselves. What purposes does this
massive cell suicide serve?
In some cases, the answers are clear. Mouse paws—and our own hands
and feet—are sculpted by apoptosis during embryonic development: they
start out as spadelike structures, and the individual fingers and toes separate
because the cells between them die (Figure 18−36). In other cases,
cells die when the structure they form is no longer needed. When a tadpole
changes into a frog at metamorphosis, the cells in its tail die, and the
tail, which is not needed in the adult frog, disappears (Figure 18−37). In
these cases, the unneeded cells die largely through apoptosis.
In adult tissues, cell death usually balances cell division, unless the tissue
is growing or shrinking. If part of the liver is removed in an adult
rat, for example, liver cells proliferate to make up the loss. Conversely,
if a rat is treated with the drug phenobarbital, which stimulates liver cell
division, the liver enlarges. However, when the phenobarbital treatment
is stopped, apoptosis in the liver greatly increases until the organ has
returned to its original size, usually within a week or so. Thus, the liver
is kept at a constant size through regulation of both the rate of cell death
and the rate of cell birth.
Apoptosis Is Mediated by an Intracellular Proteolytic
Cascade
Cells that die as a result of acute injury typically swell and burst, spewing
their contents across their neighbors, a process called cell necrosis
(Figure 18−38A). This eruption triggers a potentially damaging inflammatory
response. By contrast, a cell that undergoes apoptosis dies neatly,
without damaging its neighbors. A cell in the throes of apoptosis may
develop irregular bulges—or blebs—on its surface; but it then shrinks
and condenses (Figure 18−38B). The cytoskeleton collapses, the nuclear
envelope disassembles, and the nuclear DNA breaks up into fragments
(Movie 18.11). Most importantly, the cell surface is altered in such a
manner that it immediately attracts phagocytic cells, usually specialized
Figure 18−37 As a tadpole changes into
a frog, the cells in its tail are induced to
undergo apoptosis. All of the changes that
occur during metamorphosis, including the
induction of apoptosis in the tadpole tail,
are stimulated by an increase in thyroid
hormone in the blood.