Mechanisms of size control

Current Opinion in Genetics and Development

Volumn 11, Issue 3, 2001, Pages 279-286

  Potter, Christopher J ^a   Xu, Tian ^a  

^a HOWARD HUGHES MEDICAL INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

INSULIN RECEPTOR; INSULIN RECEPTOR SUBSTRATE 1; INSULIN RECEPTOR SUBSTRATE 2; SOMATOMEDIN; SOMATOMEDIN I; SOMATOMEDIN II; UNCLASSIFIED DRUG;

CARCINOGENESIS; CELL COUNT; CELL GROWTH; CELL PROLIFERATION; CELL SIZE; DROSOPHILA; GENE EXPRESSION; HUMAN; MUTATION; NONHUMAN; ONCOGENE MYC; ORGAN SIZE; PRIORITY JOURNAL; REGENERATION; REVIEW; TRANSPLANTATION;

DROSOPHILA;

EID: 0035371515     PISSN: 0959437X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0959-437X(00)00191-X     Document Type: Review

References (45)

1. Conlon I., Raff M. Size control in animal development. Cell. 96:1999;235-244.
2. Raff M.C. Size control: the regulation of cell numbers in animal development. Cell. 86:1996;173-175.
3. Prout T., Barker J.S. Ecological aspects of the heritability of body size in Drosophila buzzatii. Genetics. 123:1989;803-813.
4. Bryant P.J., Simpson P. Intrinsic and extrinsic control of growth in developing organs. Q Rev Biol. 59:1984;387-415.
5. Su T.T., O'Farrell P.H. Size control: cell proliferation does not equal growth. Curr Biol. 8:1998;R687-R689.
6. Dittmer J.E., Goss R.J., Dinsmore C.E. The growth of infant hearts grafted to young and adult rats. Am J Anat. 141:1974;155-160.
7. Silber S.J. Growth of baby kidneys transplanted into adults. Arch Surg. 111:1976;75-77.
8. Twitty V.C., Schwind J.L. The growth of eyes and limbs transplanted heteroplastically between two speciesof Amblystoma. J Exp Zool. 59:1931;61-86.
9. Simpson P., Berreur P., Berreur-Bonnenfant J. The initiation of pupariation in Drosophila: dependence on growth of the imaginal discs. J Embryol Exp Morphol. 57:1980;155-165.
10. Michalopoulos G.K., DeFrances M.C. Liver Regeneration. Science. 276:1997;60-66.
11. Bryant P.J. Pattern formation in the imaginal wing disc of Drosophila melanogaster: fate map, regeneration and duplication. J Exp Zool. 193:1975;49-77.
12. Lewis N.E., Rossant J. Mechanism of size regulation in mouse embryo aggregates. J Embryol Exp Morphol. 72:1982;169-181.
13. Tarkowski A.K. Experimental studies on regulation in the development of isolated blastomeres of mouse egss. Acta Theriol. 3:1959;191-267.
14. Brook W.J., Diaz-Benjumea F.J., Cohen S.M. Organizing spatial pattern in limb development. Annu Rev Cell Dev Biol. 12:1996;161-180.
15. Tabata T., Schwartz C., Gustavson E., Ali Z., Kornberg T.B. Creating a Drosophila wing de novo, the role of engrailed, and the compartment border hypothesis. Development. 121:1995;3359-3369.
16. Capdevila J., Guerrero I. Targeted expression of the signaling molecule decapentaplegic induces pattern duplications and growth alterations in Drosophila wings. EMBO J. 13:1994;4459-4468.
17. Burke R., Basler K. Dpp receptors are autonomously required for cell proliferation in the entire developing Drosophila wing. Development. 122:1996;2261-2269.
18. Theodosiou N.A., Zhang S., Wang W.Y., Xu T. Slimb coordinates wg and dpp expression in the dorsal-ventral and anterior-posterior axes during limb development. Development. 125:1998;3411-3416.
19. Vervoort M., Crozatier M., Valle D., Vincent A. The COE transcription factor Collier is a mediator of short-range Hedgehog-induced patterning of the Drosophila wing. Curr Biol. 9:1999;632-639.
20. Milan M., Campuzano S., Garcia-Bellido A. Cell cycling and patterned cell proliferation in the Drosophila wing during metamorphosis. Proc Natl Acad Sci USA. 93:1996;11687-11692.
21. Neufeld T.P., de la Cruz A.F., Johnston L.A., Edgar B.A. Coordination of growth and cell division in the Drosophila wing. Cell. 93:1998;1183-1193.
22. Weigmann K., Cohen S.M., Lehner C.F. Cell cycle progression, growth and patterning in imaginal discs despite inhibition of cell division after inactivation of Drosophila Cdc2 kinase. Development. 124:1997;3555-3563.
23. Frankenhauser G. The effects of changes in chromosome number on amphibian development. Q Rev Biol. 20:1945;20-78.
24. Xu T., Wang W., Zhang S., Stewart R.A., Yu W. Identifying tumor suppressors in genetic mosaics: the Drosophila lats gene encodes a putative protein kinase. Development. 121:1995;1053-1063.
25. Tao W., Zhang S., Turenchalk G.S., Stewart R.A., St John M.A., Chen W., Xu T. Human homologue of the Drosophila melanogaster lats tumour suppressor modulates CDC2 activity. Nat Genet. 21:1999;177-181.
26. 2 phase. It was further suggested that Ras might function partly through myc to regulate cell growth, as clonal expression of Ras could lead to an increase in myc expression.
27. Johnston L.A., Prober D.A., Edgar B.A., Eisenman R.N., Gallant P. Drosophila myc regulates cellular growth during development. Cell. 98:1999;779-790.
28. Schuhmacher M., Staege M.S., Pajic A., Polack A., Weidle U.H., Bornkamm G.W., Eick D., Kohlhuber F. Control of cell growth by c-Myc in the absence of cell division. Curr Biol. 9:1999;1255-1258.
29. Huang H., Potter C.J., Tao W., Li D.M., Brogiolo W., Hafen E., Sun H., Xu T. PTEN affects cell size, cell proliferation and apoptosis during Drosophila eye development. Development. 126:1999;5365-5372.
30. Goberdhan D.C., Paricio N., Goodman E.C., Mlodzik M., Wilson C. Drosophila tumor suppressor PTEN controls cell size and number by antagonizing the Chico/PI3-kinase signaling pathway. Genes Dev. 13:1999;3244-3258.
31. Gao X., Neufeld T.P., Pan D. Drosophila PTEN regulates cell growth and proliferation through PI3K- dependent and -independent pathways. Dev Biol. 221:2000;404-418.
32. Cantley L.C., Neel B.G. New insights into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/AKT pathway. Proc Natl Acad Sci USA. 96:1999;4240-4245.
33. Weinkove D., Leevers S.J. The genetic control of organ growth: insights from Drosophila. Curr Opin Genet Dev. 10:2000;75-80.
34. Thomas G., Hall M.N. TOR signalling and control of cell growth. Curr Opin Cell Biol. 9:1997;782-787.
35. Zhang H., Stallock J.P., Ng J.C., Reinhard C., Neufeld T.P. Regulation of cellular growth by the Drosophila target of rapamycin dTOR. Genes Dev. 14:2000;2712-2724. See annotation [36••].
36. Oldham S., Montagne J., Radimerski T., Thomas G., Hafen E. Genetic and biochemical characterization of dTOR, the Drosophila homolog of the target of rapamycin. Genes Dev. 14:2000;2689-2694. These reports describe the first animal models used to examine the effects of TOR mutations on development. Previous studies had relied on using rapamycin, which affects other processes besides TOR. dTOR mutant animals grow more slowly and are smaller than wild-type as a result of decreases in cell number and cell size. dTOR also promoted phosphorylation of S6k, and dTOR mutants could be rescued by overexpression of S6k. This links the functions of dTOR to the insulin pathway. As mutations of dTOR mimic the effects of poor growth conditions, dTOR most likely functions to coordinate organ size to environmental conditions.
37. Schmelzle T., Hall M.N. TOR, a central controller of cell growth. Cell. 103:2000;253-262.
38. Rother K.I., Accili D. Role of insulin receptors and IGF receptors in growth and development. Pediatr Nephrol. 14:2000;558-561.
39. Shioi T., Kang P.M., Douglas P.S., Hampe J., Yballe C.M., Lawitts J., Cantley L.C., Izumo S. The conserved phosphoinositide 3-kinase pathway determines heart size in mice. EMBO J. 19:2000;2537-2548. This study explores the ability of the insulin pathway to alter organ size in a mammalian system, and extends the work in Drosophila. By directing overexpression of dominant negative or activated versions of PI3K, the authors were able to either decrease or increase heart size, respectively. Consistent with studies in Drosophila, the changes in organ size were mainly as a result of changes in cell size. These results suggest that insulin signaling is a conserved mechanism to alter organ size.
40. Buratovich M.A., Bryant P.J. Enhancement of overgrowth by gene interactions in lethal(2)giant discs imaginal discs from Drosophila melanogaster. Genetics. 147:1997;657-670.
41. Teleman A.A., Cohen S.M. Dpp gradient formation in the Drosophila wing imaginal disc. Cell. 103:2000;971-980. This study takes advantage of a functional GFP-Dpp construct to image the in vivo expression pattern of an important morphogen. It was found that Dpp moves rapidly through the tissue but is quickly degraded. Interestingly, when organ size was increased by overexpressing PI3K, the regions responsive to the Dpp signal were increased, but not the expression pattern of the morphogen. These results suggest a coordinated effort between organ size and patterning.
42. Montagne J., Stewart M.J., Stocker H., Hafen E., Kozma S.C., Thomas G. Drosophila S6 kinase: a regulator of cell size. Science. 285:1999;2126-2129.
43. 1 cell-cycle components.
44. Ito N, Rubin GM: gigas, a Drosophila homolog of tuberous sclerosis gene product-2, regulates the cell cycle., Cell 1999, 96: 529-539. (Now in press) The work referred to in the text as CJ Potter et al., unpublished data, is now in press:
45. Potter CJ, Huang H, Xu T: Drosophila Tsc1 functions with Tsc2/gigas to antagonize insulin signaling in the regulation of cell growth, cell proliferation, and organ size. Cell 2001, in press. In this study, a Drosophila TSC1 mutation is described. Mutation of TSC1 results in an increase in cell size in both proliferating and differentiated cells, with a 2-3 fold increase in cell size by the adult stage. Flow cytometry analysis of mutant cells shows that this increase in cell size is not due to changes in ploidy. Organs that contain large TSC1 mutant clones are also increased in size. It is found that Drosophila TSC1 binds directly to Drosophila TSC2, and that co-overexpression of both genes is required to affect cell size, numbers, and organ size, suggesting that TSC1 and TSC2 form a functional unit. Genetic epistasis experiments also suggest that TSC1/TSC2 function as components of the insulin signaling pathway to regulate cell size.