A fertilized mouse egg and a fertilized human egg are similar in size, yet they produce animals of very different sizes. What factors in the control of cell behavior in humans and mice are responsible for these size differences? The same fundamental question can be asked for each organ and tissue in an animal’s body. What factors in the control of cell behavior explain the length of an elephant’s trunk or the size of its brain or its liver? These questions are largely unanswered, at least in part because they have received relatively little attention compared with other questions in cell and developmental biology. It is nevertheless possible to say what the ingredients of an answer must be.
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The size of an organ or organism depends mainly on its total cell mass, which depends on both the total number of cells and the size of the cells. Cell number, in turn, depends on the amounts of cell division and cell death. Organ and body size are therefore determined by three fundamental processes: cell growth, cell division, and cell death. Each is independently regulated—both by intracellular programs and by extracellular signal molecules that control these programs.
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The extracellular signal molecules that regulate cell size and cell number are generally either soluble secreted proteins, proteins bound to the surface of cells, or components of the extracellular matrix. The factors that promote organ or organism growth can be operationally divided into three major classes:
1.
Mitogens, which stimulate cell division, primarily by relieving intracellular negative controls that otherwise block progress through the cell cycle.
2.
Growth factors, which stimulate cell growth (an increase in cell mass) by promoting the synthesis of proteins and other macromolecules and by inhibiting their degradation.
3.
Survival factors, which promote cell survival by suppressing apoptosis.
Some extracellular signal molecules promote all of these processes, while others promote one or two of them. Indeed, the term growth factor is often used inappropriately to describe a factor that has any of these activities. Even worse, the term cell growth is often used to mean an increase in cell number, or cell proliferation.
In this section, we first discuss how these extracellular signals stimulate cell division, cell growth, and cell survival, thereby promoting the growth of an animal and its organs. We then consider how other extracellular signals can act in the opposite way, to inhibit cell growth or cell division or to stimulate apoptosis, thereby inhibiting organ growth.
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