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How flies get their size: genetics meets physiology

Nature Reviews Genetics volume 7, pages 907–916 (2006)Cite this article

Key Points

  • Body size affects important fitness variables such as mate selection, predation and tolerance to heat, cold and starvation. It is therefore subject to intense evolutionary selection.

  • Insects have a genetically defined 'critical weight', the attainment of which triggers hormonal signalling that leads to the cessation of feeding and then metamorphosis. Because adult insects do not grow, the critical weight, combined with growth that is accrued afterwards but before metamorphosis, during the 'interval to cessation of growth' (ICG), are thought to determine the final adult size.

  • Growth during the ICG can be substantial, accounting for as much as 80% of adult weight in Drosophila melanogaster. Growth rates are affected by diet, temperature and genotype.

  • Insulin/insulin-like growth factor signalling (IIS) and TOR signalling have been characterized as important, nutrition-dependent, positive regulators of cell growth during the ICG. As such, these signalling systems affect body size.

  • IIS and TOR activity in the prothoracic gland enhance its ability to produce ecdysone. Ecdysone in turn reduces cell growth rates and also promotes metamorphosis, and therefore acts in a negative-feedback loop in controlling body size.

  • How cell numbers and allometric growth are controlled remain poorly understood topics, as does the mechanism that determines critical weight. Progress on these problems will be important in understanding the large variations in cell numbers and body sizes that are seen among related species in the wild.

Abstract

Body size affects important fitness variables such as mate selection, predation and tolerance to heat, cold and starvation. It is therefore subject to intense evolutionary selection. Recent genetic and physiological studies in insects are providing predictions as to which gene systems are likely to be targeted in selecting for changes in body size. These studies highlight genes and pathways that also control size in mammals: insects use insulin-like growth factor (IGF) and Target of rapamycin (TOR) kinase signalling to coordinate nutrition with cell growth, and steroid and neuropeptide hormones to terminate feeding after a genetically encoded target weight is achieved. However, we still understand little about how size is actually sensed, or how organ-intrinsic size controls interface with whole-body physiology.

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Figure 1: Endocrine communication between the organs involved in growth control.
Figure 2: Control of growth during the final larval instar.

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  1. Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, B–2152, Seattle, 98109, Washington, USA

    Bruce A. Edgar

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Glossary

Fat body

A mesoderm-derived energy-storage organ that fulfils the functions that are assumed by the liver and adipose tissues in mammals.

Adipokinetic hormones

Peptide hormones with functions analogous to glucagons, produced by the corpora cardiaca, a portion of the ring gland. These hormones stimulate the mobilization of stored fat and carbohydrates from the fat body upon starvation.

Insulin-like peptides

(ILPs). Peptide hormones that are homologous to vertebrate insulins and insulin-like growth factors. ILPs are produced by medial neurosecretory cells in the brain, as well as the gut and imaginal discs. These ligands bind the insulin receptor and promote cellular glucose import, energy storage in the form of glycogen and triglycerides, and cell growth. Drosophila melanogaster has seven paralogous genes. Orthologous genes in the silk moth, Bombyx mori, are called bombyxins.

Cell autonomous

If the activity of a gene has effects only in the cells that express it, its function is said to be cell autonomous; if it causes effects in cells other than (or in addition to) those that express it, its function is cell non-autonomous.

Intracellular second messenger

A signalling molecule in cells, the concentration of which changes on the binding of an extracellular ligand to a plasma-membrane-bound receptor.

20-hydroxyecdysone

(20E). The insect moulting hormone, a steroid. The pro-hormone ecdysone is produced by the prothoracic gland. Ecdysone is then converted into active 20E by the fat body, malpighian tubules (analogous to the kidneys) and possibly the epidermis.

Juvenile hormone

(JH). A sesquiterpene produced by the corpora allata, which is a portion of the ring gland. JH promotes juvenile (larval) development and inhibits metamorphosis. It is degraded, in part, by juvenile hormone esterase, which is produced by the fat body and malpighian tubules (kidney).

Prothoracicotropic hormone

(PTTH). A neuropetide that is secreted by cells in the brain. PTTH stimulates ecdysone production by the prothoracic gland.

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Edgar, B. How flies get their size: genetics meets physiology. Nat Rev Genet 7, 907–916 (2006). https://doi.org/10.1038/nrg1989

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