Abstracts
Résumé
Les mécanismes de régulation de la taille d’un organisme ou de tissus spécifiques au sein d’un organisme sont actuellement mal connus. L’organisation et la régulation de la taille des tissus sont nécessaires au développement, à la cicatrisation des plaies et à la régénération. Une mauvaise régulation de ces mécanismes peut conduire à des anomalies congénitales ou à des cancers. Différentes informations sur les mécanismes possibles de la régulation de la taille sont exposées. La taille d’un tissu est définie par le produit de la taille des cellules constituant le tissu et par le nombre de ces cellules. La taille des cellules peut être contrôlée par les nutriments et par des facteurs sécrétés perçus par ces cellules, dépendant de la capacité maximale du génome à produire les ARNm et à les traduire en protéines. Pour contrôler le nombre de cellules dans un tissu, plusieurs exemples impliquant des facteurs sécrétés sont décrits. Une meilleure connaissance de la régulation de la taille par ces facteurs peut nous permettre de développer de nouvelles thérapies pour pallier les anomalies congénitales ou les maladies affectant la taille des tissus.
Summary
Very little is known about how the size of an organism, or a specific tissue in an organism, is regulated. Coordinating and regulating the size of tissues is necessary for proper development, wound healing, and regeneration. Defects in a tissue-size regulation mechanism could lead to birth defects or cancer. In addition, there is a strong psychological aspect to some areas of tissue size regulation, as many cosmetic surgery procedures involve enlarging or reducing the size of some body parts. This review addresses the little bit that we know about size regulation. A key concept is that the size of a tissue is the size of the component cells multiplied by the number of those cells. This breaks the size regulation problem down to two parts. The size of cells can be regulated by nutrient sensing and secreted factors, and may have an upper limit due to an upper limit of a genome’s ability to produce mRNA’s and thus proteins. To regulate the number of cells in a tissue, there are several simple theoretical models involving secreted factors. In one case, the cells can secrete a characteristic factor and the concentration of the factor will increase with the number of cells secreting it, allowing the tissue to sense its own size. In another scenario, a specific cell secretes a limited amount of a factor necessary for the survival of a target population, and this then limits the size of the target population. There are currently several examples of secreted factors that regulate tissue size, including myostatin, which regulates the amount of muscles, leptin, which regulates adipose tissue, and growth hormone and insulin-like growth factors which regulate total mass. In addition, there are factors such as the «counting factor» found in Dictyostelium that regulate the breakup of a tissue into sub-groups. A better understanding of how these factors regulate size will hopefully allow us to develop new therapeutic procedures to treat birth defects or diseases that affect tissue size.
Appendices
Références
- 1. http://surgery.org/stats.html.pages/2001.totals.html
- 2. Ivey FM, Roth SM, Ferrell RE, et al. Effects of age, gender, and myostatin genotype on the hypertrophic response to heavy resistance strength training.J Gerontol A Biol Sci Med Sci 2000; 55: M641-8.
- 3. Haldane JBS. On being the right size. In: Possible worlds and other papers. New York: Harper and Brothers, 1928: 20-8.
- 4. Schmidt-Nielsen K. Scaling why is animal size so important ? Cambridge UK: Cambridge University Press, 1984.
- 5. Neufeld TP, de la Cruz AF, Johnston LA, Edgar BA. Coordination of growth and cell division in the Drosophila wing.Cell 1998; 93: 1183-93.
- 6. Day S, Lawrence P. Measuring dimensions: the regulation of size and shape.Development 2000; 127: 2977-87.
- 7. Potter C, Xu T. Mechanisms of size control.Curr Opin Genet Dev 2001; 11: 279-86.
- 8. Newport J, Kirschner M. A major developmental transition in early Xenopus embryos. I. Characterization and timing of cellular changes at the midblastula stage.Cell 1982; 30: 675-86.
- 9. Durand B, Raff M. A cell-intrinsic timer that operates during oligodendrocyte development.BioEssays 2000; 22: 64-71.
- 10. Gomer RH. Not being the wrong size.Nat Rev CellMol Biol 2001; 2: 48-54.
- 11. Metcalf D. Restricted growth capacity of multiple spleen grafts. Transplantation 1964; 2: 387-92.
- 12. Thomas M, Langley B, Berry C, et al. Myostatin, a negative regulator of muscle growth, functions by inhibiting myoblast proliferation.J Biol Chem 2000; 275: 40235-44.
- 13. Clement K, Vaisse C, Lahlou N, et al. A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction.Nature 1998; 392: 398-401.
- 14. Weinkove D, Neufeld T, Twardzik T, Waterfield M, Leevers S. Regulation of imaginal disc cell size, cell number and organ size by Drosophila class I (A) phosphoinositide 3-kinase and its adaptor.Curr Biol 1999; 9: 1019-29.
- 15. Winkler R, Pasleau F, Boussif N, Hodzic D. The IGF system: summary and recent data.Rev Med Liege 2000; 55: 725-39.
- 16. Noguchi T. Protein nutrition and insulin-like growth factor system.Br J Nutr 2000; 2 (suppl): S241-4.
- 17. Roelfsema V, Lane M, Clark R. Insulin-like growth factor binding protein (IGFBP) displacers: relevance to the treatment of renal disease.Pediatr Nephrol 2000; 14: 584-8.
- 18. Brogiolo W, Stocker H, Ikeya T, Rintelen F, Fernandez R, Hafen E. An evolutionarily conserved function of the Drosophila insulin receptor and insulin-like peptides in growth control.Curr Biol 2001; 11: 213-21.
- 19. Montagne J, Stewart MJ, Stocker H, Hafen E, Kozma SC, Thomas G. Drosophila S6 kinase; a regulator of cell size.Science 1999; 285: 2126-9.
- 20. Brock DA, Gomer RH. A cell-counting factor regulating structure size in Dictyostelium.Genes Dev 1999; 13: 1960-9.
- 21. Roisin-Bouffay C, Jang W, Caprette DR, Gomer RH. A precise group size in Dictyostelium is generated by a cell-counting factor modulating cell-cell adhesion.Mol Cell 2000; 6: 953-9.
- 22. Tang L, Ammann R, Gao T, Gomer RH. A cell number-counting factor regulates group size in Dictyostelium by differentially modulating cAMP-induced cAMP and cGMP pulse sizes.J Biol Chem 2001; 276: 27663-9.