Regulation of imaginal disc cell size, cell number and organ size by Drosophila class I(A) phosphoinositide 3-kinase and its adaptor.
BACKGROUND
Class I(A) phosphoinositide 3-kinases (PI 3-kinases) have been implicated in the regulation of several cellular processes including cell division, cell survival and protein synthesis. The size of Drosophila imaginal discs (epithelial structures that give rise to adult organs) is maintained by factors that can compensate for experimentally induced changes in these PI 3-kinase-regulated processes. Overexpression of the gene encoding the Drosophila class I(A) PI 3-kinase, Dp110, in imaginal discs, however, results in enlarged adult organs. These observations have led us to investigate the role of Dp100 and its adaptor, p60, in the control of imaginal disc cell size, cell number and organ size.


RESULTS
Null mutations in Dp110 and p60 were generated and used to demonstrate that they are essential genes that are autonomously required for imaginal disc cells to achieve their normal adult size. In addition, modulating Dp110 activity increases or reduces cell size in the developing imaginal disc, and does so throughout the cell cycle. The inhibition of Dp110 activity reduces the rate of increase in cell number in the imaginal discs, suggesting that Dp110 normally promotes cell division and/or cell survival. Unlike direct manipulation of cell-cycle progression, manipulation of Dp110 activity in one compartment of the disc influences the size of that compartment and the size of the disc as a whole.


CONCLUSIONS
We conclude that during imaginal disc development, Dp110 and p60 regulate cell size, cell number and organ size. Our results indicate that Dp110 and p60 signalling can affect growth in multiple ways, which has important implications for the function of signalling through class I(A) PI 3-kinases.
Weinkove
D
D
Ludwig Institute for Cancer Research 91 Riding House Street, W1P 8BT, Department of Biochemistry and Molecular Biology Gower Street, London, UK.
Neufeld
T P
TP
Twardzik
T
T
Waterfield
M D
MD
Leevers
S J
SJ
D000818:Animals; D002452:Cell Count; D048429:Cell Size; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics / Q000502:physiology*; D004625:Embryo, Nonmammalian / Q000166:cytology; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D005816:Genetic Complementation Test; D019476:Insect Proteins / Q000235:genetics / Q000502:physiology*; D007527:Isoenzymes / Q000235:genetics / Q000502:physiology*; D007814:Larva / Q000166:cytology / Q000254:growth & development; D009024:Morphogenesis / Q000235:genetics / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D015398:Signal Transduction; D014921:Wings, Animal / Q000196:embryology; D018909:src Homology Domains
D029721:Drosophila Proteins; D019476:Insect Proteins; D007527:Isoenzymes; D011993:Recombinant Fusion Proteins; D019869:Phosphatidylinositol 3-Kinases; C403752:Pi3K21B protein, Drosophila