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How are the sizes of cells, organs, and bodies controlled?

Hafen E, Stocker H - PLoS Biol. (2003)

View Article: PubMed Central - PubMed

Affiliation: Zoologisches Institut at the Universität Zürich, in Zürich, Switzerland. hafen@zool.unizh.ch

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Analysis in Drosophila imaginal discs using cell clones either deficient in cell cycle progression or expressing cell cycle regulators that accelerate or slow down the cell cycle, however, have shown clearly that cell cycle progression alone is not sufficient to promote growth... In Drosophila, the reduction in wing size in S6K mutant flies or in flies raised at higher temperature is caused by a reduction in cell size ; in contrast, starvation or mutations in genes coding for insulin signaling components that mediate the starvation response affect body size and organ size by reducing cell size and cell number... The effect of insulin pathway activity on growth is largely autonomous to cells and multicellular regions, called compartments... Specific reduction of dAkt function, an essential component of the insulin signaling pathway, in either the anterior or the posterior compartment of the wing imaginal disc results in a severe reduction of the respective compartment... Astonishingly, the small compartment is properly patterned and the size and patterning of the adjacent compartment remain untouched (Figure 1), demonstrating that the insulin pathway has a profound effect on the final size of an organ without interfering with the patterning mechanism... Indeed, tkv mutant clones also survive in these regions... Therefore, brk levels do not correlate with the growth and survival potential of cells in all circumstances... Interfering with patterning mechanisms, for example, by implanting a bead soaked in the secreted factor Sonic hedgehog (Shh) into the anterior of the chick wing bud or by the ectopic expression of Hedgehog (Hh) or Dpp in the Drosophila wing, causes pattern duplications and concomitant growth... Conversely, partial loss-of-function mutations in dpp reduce wing size (Figure 2)... In contrast to the effects caused by modulating insulin pathway activity, the stimulation of growth by Dpp appears to be tightly linked with pattern formation... An attractive hypothesis put forward based on a previous model of regeneration postulates that the individual cells of an organ primordium measure the concentration gradients of specific signaling molecules, such as Dpp in the Drosophila wing disc and Shh in the vertebrate limb bud... For example, in the Drosophila eye imaginal disc, Hh regulates growth directly by controlling the expression of cyclin E, a promoter of the G1/S transition, and by cyclin D, a promoter of cell growth... Given the significant interest that has been generated in growth control, it should not be long before some of these old mysteries in biology are explained... This will not only reward us with a better understanding of this important aspect of developmental biology, but it will also provide better insight into human diseases, such as cancer, that are associated with a misregulation of cellular growth.

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The Insulin Signaling Activity Controls Organ Size in a Compartment-Specific MannerMosaic Drosophila wings with compartment-specific manipulations of dAkt function display striking size defects but normal patterning.(A) Selective reduction of dAkt function in the posterior compartment by means of FLP-mediated mitotic recombination in posterior cells (using engrailed–Gal4 to drive the expression of UAS–Flp) results in a small P compartment largely consisting of dAkt3 mutant cells. The smaller compartment size is due to fewer and smaller cells.(B) Wild-type wing for comparison.(C) Expression of dAkt in posterior cells (engrailed–Gal4 UAS–dAkt) of wings with reduced dAkt function (dAkt3) restores the size of the P compartment, whereas the A compartment remains small. The red lines mark the anterior–posterior compartment boundary. Note that similar results in the wing disc have been obtained by Teleman and Cohen (2000).
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pbio.0000086-g001: The Insulin Signaling Activity Controls Organ Size in a Compartment-Specific MannerMosaic Drosophila wings with compartment-specific manipulations of dAkt function display striking size defects but normal patterning.(A) Selective reduction of dAkt function in the posterior compartment by means of FLP-mediated mitotic recombination in posterior cells (using engrailed–Gal4 to drive the expression of UAS–Flp) results in a small P compartment largely consisting of dAkt3 mutant cells. The smaller compartment size is due to fewer and smaller cells.(B) Wild-type wing for comparison.(C) Expression of dAkt in posterior cells (engrailed–Gal4 UAS–dAkt) of wings with reduced dAkt function (dAkt3) restores the size of the P compartment, whereas the A compartment remains small. The red lines mark the anterior–posterior compartment boundary. Note that similar results in the wing disc have been obtained by Teleman and Cohen (2000).

Mentions: Changes in organ size are only partly due to changes in cell size. In Drosophila, the reduction in wing size in S6K mutant flies or in flies raised at higher temperature is caused by a reduction in cell size (Partridge et al. 1994; Montagne et al. 1999); in contrast, starvation or mutations in genes coding for insulin signaling components that mediate the starvation response affect body size and organ size by reducing cell size and cell number (Garofalo 2002). The effect of insulin pathway activity on growth is largely autonomous to cells and multicellular regions, called compartments. Specific reduction of dAkt function, an essential component of the insulin signaling pathway, in either the anterior or the posterior compartment of the wing imaginal disc results in a severe reduction of the respective compartment. Astonishingly, the small compartment is properly patterned and the size and patterning of the adjacent compartment remain untouched (Figure 1), demonstrating that the insulin pathway has a profound effect on the final size of an organ without interfering with the patterning mechanism.


How are the sizes of cells, organs, and bodies controlled?

Hafen E, Stocker H - PLoS Biol. (2003)

The Insulin Signaling Activity Controls Organ Size in a Compartment-Specific MannerMosaic Drosophila wings with compartment-specific manipulations of dAkt function display striking size defects but normal patterning.(A) Selective reduction of dAkt function in the posterior compartment by means of FLP-mediated mitotic recombination in posterior cells (using engrailed–Gal4 to drive the expression of UAS–Flp) results in a small P compartment largely consisting of dAkt3 mutant cells. The smaller compartment size is due to fewer and smaller cells.(B) Wild-type wing for comparison.(C) Expression of dAkt in posterior cells (engrailed–Gal4 UAS–dAkt) of wings with reduced dAkt function (dAkt3) restores the size of the P compartment, whereas the A compartment remains small. The red lines mark the anterior–posterior compartment boundary. Note that similar results in the wing disc have been obtained by Teleman and Cohen (2000).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC300694&req=5

pbio.0000086-g001: The Insulin Signaling Activity Controls Organ Size in a Compartment-Specific MannerMosaic Drosophila wings with compartment-specific manipulations of dAkt function display striking size defects but normal patterning.(A) Selective reduction of dAkt function in the posterior compartment by means of FLP-mediated mitotic recombination in posterior cells (using engrailed–Gal4 to drive the expression of UAS–Flp) results in a small P compartment largely consisting of dAkt3 mutant cells. The smaller compartment size is due to fewer and smaller cells.(B) Wild-type wing for comparison.(C) Expression of dAkt in posterior cells (engrailed–Gal4 UAS–dAkt) of wings with reduced dAkt function (dAkt3) restores the size of the P compartment, whereas the A compartment remains small. The red lines mark the anterior–posterior compartment boundary. Note that similar results in the wing disc have been obtained by Teleman and Cohen (2000).
Mentions: Changes in organ size are only partly due to changes in cell size. In Drosophila, the reduction in wing size in S6K mutant flies or in flies raised at higher temperature is caused by a reduction in cell size (Partridge et al. 1994; Montagne et al. 1999); in contrast, starvation or mutations in genes coding for insulin signaling components that mediate the starvation response affect body size and organ size by reducing cell size and cell number (Garofalo 2002). The effect of insulin pathway activity on growth is largely autonomous to cells and multicellular regions, called compartments. Specific reduction of dAkt function, an essential component of the insulin signaling pathway, in either the anterior or the posterior compartment of the wing imaginal disc results in a severe reduction of the respective compartment. Astonishingly, the small compartment is properly patterned and the size and patterning of the adjacent compartment remain untouched (Figure 1), demonstrating that the insulin pathway has a profound effect on the final size of an organ without interfering with the patterning mechanism.

View Article: PubMed Central - PubMed

Affiliation: Zoologisches Institut at the Universität Zürich, in Zürich, Switzerland. hafen@zool.unizh.ch

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

Analysis in Drosophila imaginal discs using cell clones either deficient in cell cycle progression or expressing cell cycle regulators that accelerate or slow down the cell cycle, however, have shown clearly that cell cycle progression alone is not sufficient to promote growth... In Drosophila, the reduction in wing size in S6K mutant flies or in flies raised at higher temperature is caused by a reduction in cell size ; in contrast, starvation or mutations in genes coding for insulin signaling components that mediate the starvation response affect body size and organ size by reducing cell size and cell number... The effect of insulin pathway activity on growth is largely autonomous to cells and multicellular regions, called compartments... Specific reduction of dAkt function, an essential component of the insulin signaling pathway, in either the anterior or the posterior compartment of the wing imaginal disc results in a severe reduction of the respective compartment... Astonishingly, the small compartment is properly patterned and the size and patterning of the adjacent compartment remain untouched (Figure 1), demonstrating that the insulin pathway has a profound effect on the final size of an organ without interfering with the patterning mechanism... Indeed, tkv mutant clones also survive in these regions... Therefore, brk levels do not correlate with the growth and survival potential of cells in all circumstances... Interfering with patterning mechanisms, for example, by implanting a bead soaked in the secreted factor Sonic hedgehog (Shh) into the anterior of the chick wing bud or by the ectopic expression of Hedgehog (Hh) or Dpp in the Drosophila wing, causes pattern duplications and concomitant growth... Conversely, partial loss-of-function mutations in dpp reduce wing size (Figure 2)... In contrast to the effects caused by modulating insulin pathway activity, the stimulation of growth by Dpp appears to be tightly linked with pattern formation... An attractive hypothesis put forward based on a previous model of regeneration postulates that the individual cells of an organ primordium measure the concentration gradients of specific signaling molecules, such as Dpp in the Drosophila wing disc and Shh in the vertebrate limb bud... For example, in the Drosophila eye imaginal disc, Hh regulates growth directly by controlling the expression of cyclin E, a promoter of the G1/S transition, and by cyclin D, a promoter of cell growth... Given the significant interest that has been generated in growth control, it should not be long before some of these old mysteries in biology are explained... This will not only reward us with a better understanding of this important aspect of developmental biology, but it will also provide better insight into human diseases, such as cancer, that are associated with a misregulation of cellular growth.

Show MeSH