Regulation of imaginal disc cell size, cell number and organ size by Drosophila class I(A) phosphoinositide 3-kinase and its adaptor

David Weinkove, Thomas P. Neufeld, Thomas Twardzik, Michael D. Waterfield, Sally J. Leevers

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262 Scopus citations

Abstract

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 Dp110 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.

Original languageEnglish (US)
Pages (from-to)1019-1029
Number of pages11
JournalCurrent Biology
Volume9
Issue number18
DOIs
StatePublished - Aug 23 1999

Bibliographical note

Funding Information:
We are very grateful to Martin Heisenberg, Dieter Maier, Anette Preiss, Jim Posakony, David Rudner, Doland Rio, Joan Hooper, Bruce Edgar, Ernst Hafen and Konrad Basler for fly stocks and Markus Noll for the genomic library. We thank Krishna Pitrola, Alan Entwistle, Mark Tumaine, Derek Davies and Heather Phillips for technical assistance and Bruce Edgar, Martin Heisenberg, Thomas Raabe, Juan Riesgo-Escovar, Ernst Hafen, Bart Vanhaesebroeck, Lindsay MacDougall and Carmen Coehlo for useful discussions. In addition, the advice of Jennifer Rohn and Helen McNeill in the preparation of this manuscript is greatly appreciated. S.J.L. is a Royal Society University Research Fellow. This work was supported by the Ludwig Institute for Cancer Research and the Royal Society.

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