The size of an organism is controlled by regulating the growth, division and death rates of cells. Whereas we know much about the mechanisms within a cell that control these parameters, how these pathways are then used to control cell number and size has remained more elusive.
Cell growth and division are often tightly coupled. For example, cyclin D mutations are implicated in size regulation in flies, mammals and plants.
When cell size is constant, initial tissue size can be controlled by regulating cell number by allowing cells to divide a certain number of times or for a specified amount of time. A counting mechanism in Xenopus laevis uses a fixed amount of a titratable factor within the egg to regulate the number of divisions. Oligodendrocytes use an intrinsic timer to stop division after a fixed time interval.
Cell number can be sensed by having cells secrete a factor that they simultaneously sense. Examples of this are found in bacteria, social amoebae and mammals. Both muscle and thyroid tissues, for example, use secreted factors as part of a negative-feedback loop to control growth.
Other secreted factors and signal-transduction pathways also regulate growth and cell division. For example, children who lack growth hormone have growth defects, which can be corrected with growth hormone treatments. Studies in mammals, flies and worms suggest a conserved role for the insulin pathway in regulating growth.
There are mechanisms that then mediate the breakup of a tissue into subgroups of defined size. For example, in Drosophila, gradients of morphogens specify subregions of the egg. In Dictyostelium, a secreted signal regulating cell–cell adhesion regulates the breakup of a tissue into subgroups.
Size regulation is a never-ending problem. Many of us worry that parts of ourselves are too big whereas other parts are too small. How organisms — and their tissues — are programmed to be a specific size, how this size is maintained, and what might cause something to become the wrong size, are key problems in developmental biology. But what are the mechanisms that regulate the size of multicellular structures?
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I thank K. Beckingham, D. Bell-Pedersen and J. Braam for helpful suggestions, D. Hatton for assistance with the manuscript and figures, and Sheila Herman for preparation of Fig. 1. R.H.G. is an Investigator of the Howard Hughes Medical Institute.
The air tubes that form the respiratory system of an insect.
- MIDBLASTULA TRANSITION
Marks the initiation of zygotic gene transcription and the end of the embryo's dependency on maternal mRNA. The mid-blastula transition also marks a lengthening of the cell cycle.
A supporting cell in the nervous system that forms a myelin sheath around axons.
A group of cells that breaks off from a column of mesoderm cells in a vertebrate embryo; the group then forms a segment of the backbone and associated structures.
An embryonic cell that becomes a muscle cell or part of a muscle cell.
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Gomer, R. Not being the wrong size. Nat Rev Mol Cell Biol 2, 48–55 (2001). https://doi.org/10.1038/35048058
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