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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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Model for the Coordinated Control of Growth and Patterning in the Drosophila Wing DiscA schematic representation of a growing (left) and a mature (right) wing disc is shown at the top. Corresponding cross-sections through the wing blade region are depicted below. The wing disc originates from the infolding of the embryonic ectoderm and consists of pseudostratified epithelial cells containing a basal–lateral side (yellow) and an apical side (red). The apical surface faces the disc lumen that is formed by the epithelium and the overlaying peripodial membrane (black), consisting of squamous epithelial cells. The morphogen and growth factor Dpp (yellow) is secreted basal–laterally by the Dpp-producing cells located anterior to the anterior–posterior compartment boundary (line through centre of wing disc). The Dpp concentration gradient from the anterior–posterior boundary to the periphery provides the anterior–posterior patterning cues. In addition, Dpp is also secreted apically into the disc lumen where is can diffuse freely. The model proposes that luminal Dpp acts as a growth-promoting factor stimulating disc growth in young discs. As the disc grows, a hypothetical growth inhibitor (blue dots) is also secreted apically and antagonizes the growth promoting activity of Dpp. Once the concentration of the inhibitor has reached a certain threshold, proliferation of wing imaginal disc cells ceases.
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pbio.0000086-g003: Model for the Coordinated Control of Growth and Patterning in the Drosophila Wing DiscA schematic representation of a growing (left) and a mature (right) wing disc is shown at the top. Corresponding cross-sections through the wing blade region are depicted below. The wing disc originates from the infolding of the embryonic ectoderm and consists of pseudostratified epithelial cells containing a basal–lateral side (yellow) and an apical side (red). The apical surface faces the disc lumen that is formed by the epithelium and the overlaying peripodial membrane (black), consisting of squamous epithelial cells. The morphogen and growth factor Dpp (yellow) is secreted basal–laterally by the Dpp-producing cells located anterior to the anterior–posterior compartment boundary (line through centre of wing disc). The Dpp concentration gradient from the anterior–posterior boundary to the periphery provides the anterior–posterior patterning cues. In addition, Dpp is also secreted apically into the disc lumen where is can diffuse freely. The model proposes that luminal Dpp acts as a growth-promoting factor stimulating disc growth in young discs. As the disc grows, a hypothetical growth inhibitor (blue dots) is also secreted apically and antagonizes the growth promoting activity of Dpp. Once the concentration of the inhibitor has reached a certain threshold, proliferation of wing imaginal disc cells ceases.

Mentions: How then does normal graded Tkv activity produce homogenous growth? One possible solution to this problem comes from the observation that Dpp in the Drosophila wing is secreted basal–laterally as well as apically (Figure 3). While Dpp secreted on the basal–lateral side in the epithelium has been detected in a concentration gradient (Teleman and Cohen 2000), Dpp secreted on the apical side accumulates in the disc lumen formed by the disc epithelium proper and the peripodial membrane, whose cells also secrete Dpp (Gibson et al. 2002). It is tempting to speculate that Dpp in the lumen functions as a general growth-promoting factor, while Dpp secreted in a graded fashion from the basal–lateral side induces pattern formation. A growth-promoting function has been suggested for the luminally produced Dpp (Gibson et al. 2002). This model implies that Dpp received on the apical side of the cell triggers a different cellular response (growth, survival, or both) than Dpp received on the basal–lateral side (patterning) and would probably require an unequal distribution of Dpp receptors or signaling components along the apical–basal axis of the cell.


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

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

Model for the Coordinated Control of Growth and Patterning in the Drosophila Wing DiscA schematic representation of a growing (left) and a mature (right) wing disc is shown at the top. Corresponding cross-sections through the wing blade region are depicted below. The wing disc originates from the infolding of the embryonic ectoderm and consists of pseudostratified epithelial cells containing a basal–lateral side (yellow) and an apical side (red). The apical surface faces the disc lumen that is formed by the epithelium and the overlaying peripodial membrane (black), consisting of squamous epithelial cells. The morphogen and growth factor Dpp (yellow) is secreted basal–laterally by the Dpp-producing cells located anterior to the anterior–posterior compartment boundary (line through centre of wing disc). The Dpp concentration gradient from the anterior–posterior boundary to the periphery provides the anterior–posterior patterning cues. In addition, Dpp is also secreted apically into the disc lumen where is can diffuse freely. The model proposes that luminal Dpp acts as a growth-promoting factor stimulating disc growth in young discs. As the disc grows, a hypothetical growth inhibitor (blue dots) is also secreted apically and antagonizes the growth promoting activity of Dpp. Once the concentration of the inhibitor has reached a certain threshold, proliferation of wing imaginal disc cells ceases.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC300694&req=5

pbio.0000086-g003: Model for the Coordinated Control of Growth and Patterning in the Drosophila Wing DiscA schematic representation of a growing (left) and a mature (right) wing disc is shown at the top. Corresponding cross-sections through the wing blade region are depicted below. The wing disc originates from the infolding of the embryonic ectoderm and consists of pseudostratified epithelial cells containing a basal–lateral side (yellow) and an apical side (red). The apical surface faces the disc lumen that is formed by the epithelium and the overlaying peripodial membrane (black), consisting of squamous epithelial cells. The morphogen and growth factor Dpp (yellow) is secreted basal–laterally by the Dpp-producing cells located anterior to the anterior–posterior compartment boundary (line through centre of wing disc). The Dpp concentration gradient from the anterior–posterior boundary to the periphery provides the anterior–posterior patterning cues. In addition, Dpp is also secreted apically into the disc lumen where is can diffuse freely. The model proposes that luminal Dpp acts as a growth-promoting factor stimulating disc growth in young discs. As the disc grows, a hypothetical growth inhibitor (blue dots) is also secreted apically and antagonizes the growth promoting activity of Dpp. Once the concentration of the inhibitor has reached a certain threshold, proliferation of wing imaginal disc cells ceases.
Mentions: How then does normal graded Tkv activity produce homogenous growth? One possible solution to this problem comes from the observation that Dpp in the Drosophila wing is secreted basal–laterally as well as apically (Figure 3). While Dpp secreted on the basal–lateral side in the epithelium has been detected in a concentration gradient (Teleman and Cohen 2000), Dpp secreted on the apical side accumulates in the disc lumen formed by the disc epithelium proper and the peripodial membrane, whose cells also secrete Dpp (Gibson et al. 2002). It is tempting to speculate that Dpp in the lumen functions as a general growth-promoting factor, while Dpp secreted in a graded fashion from the basal–lateral side induces pattern formation. A growth-promoting function has been suggested for the luminally produced Dpp (Gibson et al. 2002). This model implies that Dpp received on the apical side of the cell triggers a different cellular response (growth, survival, or both) than Dpp received on the basal–lateral side (patterning) and would probably require an unequal distribution of Dpp receptors or signaling components along the apical–basal axis of the cell.

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
Related in: MedlinePlus