Development is, literally, the journey of a life time, and it is a trip still as mysterious as it is remarkable. Despite new methods to probe how an animal or plant forms from a single cell, biologists have much to learn about the unimaginably complex process. To identify some of the field’s persistent riddles, Senior Editors Beverly Purnell and Stella Hurtley and the news staff of Science have consulted with developmental biologists on our Board of Reviewing Editors and elsewhere. The mysteries offered here are a humbling reminder that our knowledge of development remains to a great extent embryonic.
Developmental biologists have found dozens of proteins and genes that play a role in the growth of plants and animals, such as imaginal discs and Hippo and morphogenetic proteins, but not what determines organ size.
A variety of experiments have shown that both the size of imaginal discs and the organs they form are very tightly controlled. When researchers transplant the wing imaginal disc from an early fly larva to a later one or vice versa, the wing still reaches normal size despite having different growing times. If researchers kill a portion of the imaginal disc cells with radiation or other techniques, the insect can boost cell division and still form a normal-size adult. If a fly receives just a fragment of a disc as a transplant, the animal won’t move to the next stage of development until the disc has reached the correct size—pausing overall development to allow the disc to catch up. The transplanted disc “will know what size it should be,” says developmental biologist Savraj Grewal of the University of Calgary in Canada.
Many researchers suspect that a developing organ somehow senses the mechanical forces on its growing and dividing cells. One theory is that relative crowding and stretching of cells helps determine whether a cell continues to divide or stops.
The size of an organ depends not only on how many cells it has, but also how big those cells are. Some developing organs—plant leaves, for example, and fruit fly wings—can compensate when fewer cells are available by making the individual cells larger. How a leaf knows when to expand its cells is also unclear, says Hirokazu Tsukaya, a developmental biologist at the University of Tokyo who was among the first to characterize the phenomenon in leaves. He and his team have evidence that some sort of cell-to-cell communication drives the process. Here, too, the evidence suggests that a plant doesn’t count cells but can somehow assess the overall size of a leaf, says plant biologist Beth Krizek of the University of South Carolina in Columbia. “But the mechanism of how that works is another mystery.”
The size of tissues, and ultimately an overall organism, also clearly depends on signals from the environment, which researchers call extrinsic factors. Those size control systems are connected to, but different from, the intrinsic systems that help ensure an organism is correctly proportioned. In plants, growth can be especially sensitive to such outside factors, Krizek notes, because they can’t move. Plants growing in shade, for example, concentrate on stem growth—to reach the sun—instead of leaf development. In animals, the amount of nutrition available can strongly influence the final size of some organs. One dramatic instance is the horn on a rhinoceros beetle. The horn is a sexually selected trait; males with bigger horns get access to more females. Recent studies have shown that the size of the horn is particularly sensitive to insulin signaling, which is related to the beetle’s nutrition. That, in turn, signals the animal’s overall fitness (Science, 27 July 2012, p. 408).
The problem of size control is still a fundamental one for developmental biologists, says Peter Lawrence of the University of Cambridge in the United Kingdom. Together with shape, size “is the material that evolution largely works on.” But the field is still mostly in the dark. Despite hundreds of papers on what happens when the Hippo signaling pathway is interrupted, Lawrence notes, what scientists really need to understand is what it does when it is working properly. “That is not something we know.”