How flies get their size: genetics meets physiology

• Published in: Nature reviews. Genetics Vol. 7; no. 12; pp. 907 - 916
• Main Author: Edgar, Bruce A.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.12.2006; Nature Publishing Group
• Subjects: Adults; Agriculture; Animal Genetics and Genomics; Animals; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Body Size - genetics; Body Size - physiology; Butterflies & moths; Cancer Research; Cell growth; Cell Size; Drosophila melanogaster - anatomy & histology; Drosophila Proteins - physiology; Food; Fundamental and applied biological sciences. Psychology; Gene Function; Genetics of eukaryotes. Biological and molecular evolution; Hormones; Human Genetics; Insect Hormones - physiology; Insects; Insulin; Insulin-like growth factors; Nutrition; Peptides; Phosphatidylinositol 3-Kinases - physiology; Physiology; Protein Kinases; review-article; Somatomedins - physiology; TOR Serine-Threonine Kinases; Triglycerides; Genetics; Physiology
• ISSN: 1471-0056; 1471-0064
• DOI: 10.1038/nrg1989

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. Both genetic and physiological studies are contributing to our understanding of insect body size, a trait that affects fitness in many ways and is therefore subject to intense selection. Many of the genes that determine body size in insects have similar roles in mammals. 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.