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Cell-autonomous regulation of cell and organ growth in Drosophila by Akt/PKB

Abstract

Organismal size is determined by a tightly regulated mechanism that coordinates cell growth, cell proliferation and cell death. The Drosophila insulin receptor/Chico/Dp110 pathway regulates cell and organismal size. Here we show that genetic manipulation of the phosphoinositide-3-OH-kinase-dependent serine/threonine protein kinase Akt (protein kinase B) during development of the Drosophila imaginal disc affects cell and organ size in an autonomous manner. Ectopic expression of Akt does not affect cell-fate determination, apoptosis or proliferation rates in imaginal discs. Thus, Akt appears to stimulate intracellular pathways that specifically regulate cell and compartment size independently of cell proliferation in vivo.

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Figure 1: Activation of the insulin receptor stimulates Dakt1 kinase activity in a PI(3)K-dependent manner.
Figure 2: Dakt1 loss-of-function and overexpression phenotypes in the Drosophila eye.
Figure 3: Dakt1 expression does not affect photoreceptor differentiation and apoptosis during eye development.
Figure 4: Dakt1 expression during wing disc development affects compartment size in the wing imaginal disc cell-autonomously.
Figure 5: Dakt1 expression during wing disc development affects compartment size in the adult wing.
Figure 6: Dakt1 increases compartment size by affecting cell growth but not cell number.
Figure 7: Dakt1 expression does not affect cell-cycle progression.
Figure 8: Dakt1 increases clonal size by increasing cell size but not cell number.

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Acknowledgements

We thank A. Manoukian, M. Fortini, H. Steller and B. Edgar for providing fly stocks; R. Nusse for providing the pMK33 vector; Y. Ye for help with microinjections; and K. Quinn, N. Budnik and N. Brake for expert technical assistance. J.V. is supported by a Spanish Ministry of Science and Education Postdoctoral Fellowship. E.L.W. is supported by NIH grant GM 55162.

Correspondence and requests for materials should be addressed to M.J.B.

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Correspondence to Morris J. Birnbaum.

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Verdu, J., Buratovich, M., Wilder, E. et al. Cell-autonomous regulation of cell and organ growth in Drosophila by Akt/PKB. Nat Cell Biol 1, 500–506 (1999). https://doi.org/10.1038/70293

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