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The Drosophila sterile-20 kinase slik controls cell proliferation and apoptosis during imaginal disc development.

Hipfner DR, Cohen SM - PLoS Biol. (2003)

Bottom Line: Tumor-like tissue overgrowth results when apoptosis is prevented.Activation of Raf can compensate for the lack of Slik and support cell survival, but activation of ERK cannot.We suggest that Slik mediates growth and survival cues to promote cell proliferation and control cell survival during Drosophila development.

View Article: PubMed Central - PubMed

Affiliation: European Molecular Biology Laboratory, Heidelberg, Germany.

ABSTRACT
Cell proliferation and programmed cell death are closely controlled during animal development. Proliferative stimuli generally also induce apoptosis, and anti-apoptotic factors are required to allow net cell proliferation. Genetic studies in Drosophila have led to identification of a number of genes that control both processes, providing new insights into the mechanisms that coordinate cell growth, proliferation, and death during development and that fail to do so in diseases of cell proliferation. We present evidence that the Drosophila Sterile-20 kinase Slik promotes cell proliferation and controls cell survival. At normal levels, Slik provides survival cues that prevent apoptosis. Cells deprived of Slik activity can grow, divide, and differentiate, but have an intrinsic survival defect and undergo apoptosis even under conditions in which they are not competing with normal cells for survival cues. Like some oncogenes, excess Slik activity stimulates cell proliferation, but this is compensated for by increased cell death. Tumor-like tissue overgrowth results when apoptosis is prevented. We present evidence that Slik acts via Raf, but not via the canonical ERK pathway. Activation of Raf can compensate for the lack of Slik and support cell survival, but activation of ERK cannot. We suggest that Slik mediates growth and survival cues to promote cell proliferation and control cell survival during Drosophila development.

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slik Mutant Clones in Adult Wings(A and B) Cuticle preparations of adult wings from w f36a hs-FLP1/Y; FRT42D P(f+) P(f+) M(2)l2/FRT42D slik1 larvae.(A) Adult wing from a larva not subjected to heat shock to induce clones.(B) Wing with large homozygous Minute+ slik1 mutant clones. Note the small size of the wing and the vesicles of black necrotic tissue between the layers of the wing.(C) Detail of a clone in the wing margin. Mutant cells, marked by forked, differentiate as normal wing margin bristles (arrows).(D) Detail of a clone in the wing blade. Mutant cells differentiate as normal wing blade and wing vein cells. The boundary of the clone in the vein is indicated by the dashed red line.(E and F) slikKG04837/slik1 wings. In (E), the arrow indicates a small vesicle in a mildly affected wing.
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pbio.0000035-g005: slik Mutant Clones in Adult Wings(A and B) Cuticle preparations of adult wings from w f36a hs-FLP1/Y; FRT42D P(f+) P(f+) M(2)l2/FRT42D slik1 larvae.(A) Adult wing from a larva not subjected to heat shock to induce clones.(B) Wing with large homozygous Minute+ slik1 mutant clones. Note the small size of the wing and the vesicles of black necrotic tissue between the layers of the wing.(C) Detail of a clone in the wing margin. Mutant cells, marked by forked, differentiate as normal wing margin bristles (arrows).(D) Detail of a clone in the wing blade. Mutant cells differentiate as normal wing blade and wing vein cells. The boundary of the clone in the vein is indicated by the dashed red line.(E and F) slikKG04837/slik1 wings. In (E), the arrow indicates a small vesicle in a mildly affected wing.

Mentions: Despite the elevated rate of apoptosis observed in mutant clones and discs, many slik mutant cells survived and were integrated normally in the disc epithelium. To assess the developmental capacity of these cells, we examined adult wings bearing large Minute+ slik1 mutant clones generated at 60 ± 12 h. Most of these wings curved upward or downward to varying degrees, suggesting that there were differences in the sizes of the dorsal and ventral surfaces of the wing blade. In more severe cases, the wings were small and contained vesicles of blackened tissue (Figure 5A and 5B). These vesicles may derive from cells extruded on the basal side of the epithelium, which come to lie between the two layers of the wing blade. slik mutant cells that remained in the epithelium differentiated into morphologically normal wing blade cells, margin bristles, and wing veins (Figure 5C and 5D). Mutant cells were the same size as wild-type cells.


The Drosophila sterile-20 kinase slik controls cell proliferation and apoptosis during imaginal disc development.

Hipfner DR, Cohen SM - PLoS Biol. (2003)

slik Mutant Clones in Adult Wings(A and B) Cuticle preparations of adult wings from w f36a hs-FLP1/Y; FRT42D P(f+) P(f+) M(2)l2/FRT42D slik1 larvae.(A) Adult wing from a larva not subjected to heat shock to induce clones.(B) Wing with large homozygous Minute+ slik1 mutant clones. Note the small size of the wing and the vesicles of black necrotic tissue between the layers of the wing.(C) Detail of a clone in the wing margin. Mutant cells, marked by forked, differentiate as normal wing margin bristles (arrows).(D) Detail of a clone in the wing blade. Mutant cells differentiate as normal wing blade and wing vein cells. The boundary of the clone in the vein is indicated by the dashed red line.(E and F) slikKG04837/slik1 wings. In (E), the arrow indicates a small vesicle in a mildly affected wing.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC261876&req=5

pbio.0000035-g005: slik Mutant Clones in Adult Wings(A and B) Cuticle preparations of adult wings from w f36a hs-FLP1/Y; FRT42D P(f+) P(f+) M(2)l2/FRT42D slik1 larvae.(A) Adult wing from a larva not subjected to heat shock to induce clones.(B) Wing with large homozygous Minute+ slik1 mutant clones. Note the small size of the wing and the vesicles of black necrotic tissue between the layers of the wing.(C) Detail of a clone in the wing margin. Mutant cells, marked by forked, differentiate as normal wing margin bristles (arrows).(D) Detail of a clone in the wing blade. Mutant cells differentiate as normal wing blade and wing vein cells. The boundary of the clone in the vein is indicated by the dashed red line.(E and F) slikKG04837/slik1 wings. In (E), the arrow indicates a small vesicle in a mildly affected wing.
Mentions: Despite the elevated rate of apoptosis observed in mutant clones and discs, many slik mutant cells survived and were integrated normally in the disc epithelium. To assess the developmental capacity of these cells, we examined adult wings bearing large Minute+ slik1 mutant clones generated at 60 ± 12 h. Most of these wings curved upward or downward to varying degrees, suggesting that there were differences in the sizes of the dorsal and ventral surfaces of the wing blade. In more severe cases, the wings were small and contained vesicles of blackened tissue (Figure 5A and 5B). These vesicles may derive from cells extruded on the basal side of the epithelium, which come to lie between the two layers of the wing blade. slik mutant cells that remained in the epithelium differentiated into morphologically normal wing blade cells, margin bristles, and wing veins (Figure 5C and 5D). Mutant cells were the same size as wild-type cells.

Bottom Line: Tumor-like tissue overgrowth results when apoptosis is prevented.Activation of Raf can compensate for the lack of Slik and support cell survival, but activation of ERK cannot.We suggest that Slik mediates growth and survival cues to promote cell proliferation and control cell survival during Drosophila development.

View Article: PubMed Central - PubMed

Affiliation: European Molecular Biology Laboratory, Heidelberg, Germany.

ABSTRACT
Cell proliferation and programmed cell death are closely controlled during animal development. Proliferative stimuli generally also induce apoptosis, and anti-apoptotic factors are required to allow net cell proliferation. Genetic studies in Drosophila have led to identification of a number of genes that control both processes, providing new insights into the mechanisms that coordinate cell growth, proliferation, and death during development and that fail to do so in diseases of cell proliferation. We present evidence that the Drosophila Sterile-20 kinase Slik promotes cell proliferation and controls cell survival. At normal levels, Slik provides survival cues that prevent apoptosis. Cells deprived of Slik activity can grow, divide, and differentiate, but have an intrinsic survival defect and undergo apoptosis even under conditions in which they are not competing with normal cells for survival cues. Like some oncogenes, excess Slik activity stimulates cell proliferation, but this is compensated for by increased cell death. Tumor-like tissue overgrowth results when apoptosis is prevented. We present evidence that Slik acts via Raf, but not via the canonical ERK pathway. Activation of Raf can compensate for the lack of Slik and support cell survival, but activation of ERK cannot. We suggest that Slik mediates growth and survival cues to promote cell proliferation and control cell survival during Drosophila development.

Show MeSH
Related in: MedlinePlus