Cell Size Control
David A Guertin, Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA David M Sabatini, Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA Growth in biological systems is defined as the accumulation of mass, which leads to an increase in size. In this article, we discuss how cells, organs, and organisms normally control growth, and how deregulated growth can lead to a variety of pathological conditions.
. Introduction . Increasing Cell Mass by Building New Protein . Human Diseases of Cell Growth . Coordinating Cell Growth and Cell Division . Organ and Organism Growth in Humans . Hypertrophy versus Hyperplasia . How is Organ Size and Body Size Coordinated?
Controlling growth in cells organs and organisms
A major unanswered question in biology is – how do living organisms control their size? There are dramatic diﬀerences in the size of animals; for instance, blue whales, the largest animal that has ever lived, can grow up to 110 ft in length and weigh over 360 000 pounds, while the fairyﬂy, the smallest insect, is only 0.01 in. in length. Even within a species, there are variations in size. Consider humans, our average heights and weights change as we grow, and are also diﬀerent between age groups, race and gender. Although there is such variation among organisms, the organs and appendages of each individual are normally in proportion with the body as a whole. What controls the size of organisms and their components? For the most part, the answer lies in the genes. Genetic variations control the size to which organs or organisms can grow. Genes control the synthesis and transport of hormones and growth factors, which act on diﬀerent tissues to control overall body growth. However, environmental factors are also important. A good laboratory example is the developing fruitﬂy, which when fed a nutrient-restricted diet, develops normally, but is signiﬁcantly smaller than ﬂies fed a normal diet. This can also be seen in humans where malnourished children develop a growth deﬁciency. Thus, factors such as nutrition impinge on the genetic programme to control animal size. The overall size of any animal or organ depends on the number and size of its cells. The average animal cell size is approximately 10–20 mm in diameter. Such small size results in a large surface area-to-volume ratio that allows for eﬃcient transport of materials in and out of cells. If cells were too large, transport would be ineﬃcient and incapable of supporting the metabolic demands of the cell. Thus, large organisms, like elephants, are made of more cells, not bigger cells. Within our bodies, there are 20–30 trillion cells, which make up approximately 200 diﬀerent varieties. While the average cell size is small, the range of cell sizes is diverse (Figure 1). The human oocyte grows up to 100 mm in diameter. Neurons, like Purkinje cells of the brain and motor neurons can grow much larger than the average cell. Some Schwann cells, which are companion cells for nerve cells,
. Genetics, Nutrition, Environment and Body Growth . Plant Cell Growth . Summary . Acknowledgements
are 30–60 mm in embryonic life and grow coordinately with the growing axon during development, potentially reaching up to 1 mm in adult life. Size variation can be found in cells circulating in the blood; for instance, neutrophils are 10 mm in diameter while macrophages are 20–30 mm in diameter. These variations in cell size raise a fundamental biological question: Do cells regulate their growth? Cell growth is the process of building mass to increase size, not to be confused with cell division, the process whereby one cell divides into two. All cells grow to a ﬁnal size, and in every passage through the division cycle, cells must grow to an optimal size prior to dividing. How do cells increase their mass? Cell size can be proportional...
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What controls animal growth? In recent years it has become increasingly clear that cells have an intracellular mechanism to sense environmental growth conditions. If conditions permit growth, the signalling centre will trigger mass accumulation by initiating synthesis of new protein. TOR is a central component of this signalling centre and is directly responsible for activating the protein synthesis machinery. Thus, inhibitors of TOR may be promising agents for treating diseases of abnormal growth like cancer. Controlling growth is more complex in organs and organisms, where increases in cell number, cell size or both, as well as cell death, contribute to organ size. In some tissues, organ mass can only be increased by increasing cell size, called hypertrophy. Hypertrophy can result from a
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