Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

GROWTH
1193
Summary
Animal development involves dramatic cell movements, including the guided
migration of individual cells, the adhesion and repulsion of groups of cells, and the
complex extension, branching, or rolling up of epithelial tissues. Migrant cells, such
as those of the neural crest, break loose from their original neighbors and travel
through the embryo to colonize new sites. Many migrant cells, including primordial
germ cells, are guided by chemotaxis dependent on the receptor CXCR4 and
its ligand CXCL12. In general, cells that have similar adhesion molecules on their
surfaces cohere and tend to segregate from other cell groups with different surface
properties. Selective cell–cell adhesion is often mediated by cadherins; repulsion is
often driven by ephrin–Eph signaling. Within an epithelial sheet, cells can rearrange
themselves to drive epithelial convergence and extension, as in gastrulation. Many
movements are coordinated through a Wnt-dependent planar-polarity signaling
pathway that is also responsible for orienting cells correctly in various types of epithelium.
Elaborate branched tubular structures, such as the airways of the lung,
are generated through bidirectional signaling between an epithelial bud and the
mesenchyme that it invades, in a process called branching morphogenesis. Epithelial
tubes and vesicles can originate in various ways, most simply by the rolling up
and pinching off of a segment of epithelium, as in the formation of the neural tube.
GROWTH
One of the most fundamental aspects of animal development is one we know
surprisingly little about—how the size of an animal or an organ is determined.
Why, for example, do we grow to be so much larger than a mouse? Even within a
species, size can vary greatly; a Great Dane, for instance, can weigh over 40 times
more than a Chihuahua (Figure 21–57).
Three variables define the size of an organ or organism: the number of cells,
the size of the cells, and the quantity of extracellular material per cell. Size differences
can arise from changes in any of these factors (Figure 21–58). If we compare
a mouse with a human, for example, we find that the difference lies chiefly in the
number of cells, there being roughly 3000 times more cells in a human, corresponding
to a body that is roughly 3000 times more massive. Wild and cultivated
species of food plants, on the other hand, often differ in body size chiefly because
of differences of cell size.
The challenge, therefore, is to understand how cell numbers, cell size, and
extracellular matrix production are regulated. First of all, we need to identify the
signals that drive or inhibit growth. Then we need to discover how the signals
themselves are regulated. In many cases, the size of an organ or of the body as a
whole seems to be controlled homeostatically, so that the correct size is reached
and maintained even in the face of drastic disturbances. This suggests that the
developing structure somehow senses its own size and uses this information to
regulate the signals for its own growth or shrinkage. In most cases, the nature of
this feedback control remains a profound mystery.
In other cases, the duration of growth and the final size seem to be dictated
by intracellular programs that take no cognizance of the size the structure has
attained. These intracellular programs, too, present many mysteries, as we saw in
our discussion of developmental timing. Very often, it seems, the sizes and proportions
of body parts must depend on combinations of size-measuring feedback
controls and intracellular programs, as well as on environmental influences such
as nutrition.
The variation in control strategies is nicely illustrated by some classic transplantation
experiments. If several fetal thymus glands are transplanted into a
developing mouse, each grows to its characteristic adult size. In contrast, if multiple
fetal spleens are transplanted, each ends up smaller than normal, but collectively
they grow to the size of one adult spleen. Thus, thymus growth is regulated
by local mechanisms intrinsic to the individual organ, whereas spleen growth is
controlled by a feedback mechanism that senses the quantity of spleen tissue in
the body as a whole. In neither case is the mechanism known.
Figure 21–57 Members of the same
species can have dramatically different
sizes. The Chihuahua weighs
2–5 kilograms, whereas a Great Dane
weighs 45–90 kilograms. (Courtesy of
Deanne MBoC6 Fitzmaurice.) n22.226/22.55