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Loss of flfl Triggers JNK-Dependent Cell Death in Drosophila.

Huang J, Xue L - Biomed Res Int (2015)

Bottom Line: In this study, we performed gain-of-function and loss-of-function analysis in Drosophila and identified flfl as a negative regulator of JNK pathway-mediated cell death.These data report for the first time an essential physiological function of flfl in maintaining tissue homeostasis and organ development.As the JNK signaling pathway has been evolutionary conserved from fly to human, a similar role of PP4R3 in JNK-mediated physiological process is speculated.

View Article: PubMed Central - PubMed

Affiliation: Institute of Intervention Vessel, Shanghai 10th People's Hospital, Shanghai Key Laboratory of Signaling and Diseases Research, School of Life Science and Technology, Tongji University, 1239 Siping Road, Shanghai 200092, China.

ABSTRACT
falafel (flfl) encodes a Drosophila homolog of human SMEK whose in vivo functions remain elusive. In this study, we performed gain-of-function and loss-of-function analysis in Drosophila and identified flfl as a negative regulator of JNK pathway-mediated cell death. While ectopic expression of flfl suppresses TNF-triggered JNK-dependent cell death, loss of flfl promotes JNK activation and cell death in the developing eye and wing. These data report for the first time an essential physiological function of flfl in maintaining tissue homeostasis and organ development. As the JNK signaling pathway has been evolutionary conserved from fly to human, a similar role of PP4R3 in JNK-mediated physiological process is speculated.

No MeSH data available.


Related in: MedlinePlus

Loss of flfl induces JNK pathway activation and cell death in wing development. Drosophila 3rd instar wing discs with AO ((a)–(c)) and X-Gal staining ((d)–(f)) are shown. Knocking down flfl in the posterior compartment of wing discs by en-Gal4 induced extensively cell death (c) and puc-LacZ expression (f), while expressing a GFP RNAi failed to do so ((b) and (d)). en-Gal4 ((a) and (d)) served as controls. Dashed line indicates the anterior-posterior boundary of wing discs ((c) and (f)). Anterior boundary is to the left in all panels. Genotypes: en-Gal4/+ (a); en-Gal4/UAS-GFP-IR (b); en-Gal4/UAS-flfl-IR (c); en-Gal4/+; pucE69/+ (d); en-Gal4/+; pucE69/UAS-GFP-IR (e); en-Gal4/+; pucE69/UAS-flfl-IR (f). SMEK1 (g) and DUSP1 (h) relative expression level in invasive breast carcinoma stroma compared to normal tissue in Finak Breast dataset are shown. Reporter: A_24_P36961 and A_23_P110712 are probes used in the study to detect SMEK1 and DUSP1, respectively. Breast stands for normal samples. The number in the parenthesis represents the total number of samples.
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fig4: Loss of flfl induces JNK pathway activation and cell death in wing development. Drosophila 3rd instar wing discs with AO ((a)–(c)) and X-Gal staining ((d)–(f)) are shown. Knocking down flfl in the posterior compartment of wing discs by en-Gal4 induced extensively cell death (c) and puc-LacZ expression (f), while expressing a GFP RNAi failed to do so ((b) and (d)). en-Gal4 ((a) and (d)) served as controls. Dashed line indicates the anterior-posterior boundary of wing discs ((c) and (f)). Anterior boundary is to the left in all panels. Genotypes: en-Gal4/+ (a); en-Gal4/UAS-GFP-IR (b); en-Gal4/UAS-flfl-IR (c); en-Gal4/+; pucE69/+ (d); en-Gal4/+; pucE69/UAS-GFP-IR (e); en-Gal4/+; pucE69/UAS-flfl-IR (f). SMEK1 (g) and DUSP1 (h) relative expression level in invasive breast carcinoma stroma compared to normal tissue in Finak Breast dataset are shown. Reporter: A_24_P36961 and A_23_P110712 are probes used in the study to detect SMEK1 and DUSP1, respectively. Breast stands for normal samples. The number in the parenthesis represents the total number of samples.

Mentions: To investigate the physiological functions of flfl in wing development, we specifically knocked down flfl in the posterior compartment of wing discs by engrailed-Gal4 (en-Gal4) and checked cell death with AO staining. We found that loss of flfl triggered extensive cell death in the posterior compartment of wing discs (Figure 4(c)), compared with the en-Gal4 control (Figure 4(a)) and en > GFP-IR (Figure 4(b)). These results suggest that flfl is physiologically required for cell survival in Drosophila wing development.


Loss of flfl Triggers JNK-Dependent Cell Death in Drosophila.

Huang J, Xue L - Biomed Res Int (2015)

Loss of flfl induces JNK pathway activation and cell death in wing development. Drosophila 3rd instar wing discs with AO ((a)–(c)) and X-Gal staining ((d)–(f)) are shown. Knocking down flfl in the posterior compartment of wing discs by en-Gal4 induced extensively cell death (c) and puc-LacZ expression (f), while expressing a GFP RNAi failed to do so ((b) and (d)). en-Gal4 ((a) and (d)) served as controls. Dashed line indicates the anterior-posterior boundary of wing discs ((c) and (f)). Anterior boundary is to the left in all panels. Genotypes: en-Gal4/+ (a); en-Gal4/UAS-GFP-IR (b); en-Gal4/UAS-flfl-IR (c); en-Gal4/+; pucE69/+ (d); en-Gal4/+; pucE69/UAS-GFP-IR (e); en-Gal4/+; pucE69/UAS-flfl-IR (f). SMEK1 (g) and DUSP1 (h) relative expression level in invasive breast carcinoma stroma compared to normal tissue in Finak Breast dataset are shown. Reporter: A_24_P36961 and A_23_P110712 are probes used in the study to detect SMEK1 and DUSP1, respectively. Breast stands for normal samples. The number in the parenthesis represents the total number of samples.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4637051&req=5

fig4: Loss of flfl induces JNK pathway activation and cell death in wing development. Drosophila 3rd instar wing discs with AO ((a)–(c)) and X-Gal staining ((d)–(f)) are shown. Knocking down flfl in the posterior compartment of wing discs by en-Gal4 induced extensively cell death (c) and puc-LacZ expression (f), while expressing a GFP RNAi failed to do so ((b) and (d)). en-Gal4 ((a) and (d)) served as controls. Dashed line indicates the anterior-posterior boundary of wing discs ((c) and (f)). Anterior boundary is to the left in all panels. Genotypes: en-Gal4/+ (a); en-Gal4/UAS-GFP-IR (b); en-Gal4/UAS-flfl-IR (c); en-Gal4/+; pucE69/+ (d); en-Gal4/+; pucE69/UAS-GFP-IR (e); en-Gal4/+; pucE69/UAS-flfl-IR (f). SMEK1 (g) and DUSP1 (h) relative expression level in invasive breast carcinoma stroma compared to normal tissue in Finak Breast dataset are shown. Reporter: A_24_P36961 and A_23_P110712 are probes used in the study to detect SMEK1 and DUSP1, respectively. Breast stands for normal samples. The number in the parenthesis represents the total number of samples.
Mentions: To investigate the physiological functions of flfl in wing development, we specifically knocked down flfl in the posterior compartment of wing discs by engrailed-Gal4 (en-Gal4) and checked cell death with AO staining. We found that loss of flfl triggered extensive cell death in the posterior compartment of wing discs (Figure 4(c)), compared with the en-Gal4 control (Figure 4(a)) and en > GFP-IR (Figure 4(b)). These results suggest that flfl is physiologically required for cell survival in Drosophila wing development.

Bottom Line: In this study, we performed gain-of-function and loss-of-function analysis in Drosophila and identified flfl as a negative regulator of JNK pathway-mediated cell death.These data report for the first time an essential physiological function of flfl in maintaining tissue homeostasis and organ development.As the JNK signaling pathway has been evolutionary conserved from fly to human, a similar role of PP4R3 in JNK-mediated physiological process is speculated.

View Article: PubMed Central - PubMed

Affiliation: Institute of Intervention Vessel, Shanghai 10th People's Hospital, Shanghai Key Laboratory of Signaling and Diseases Research, School of Life Science and Technology, Tongji University, 1239 Siping Road, Shanghai 200092, China.

ABSTRACT
falafel (flfl) encodes a Drosophila homolog of human SMEK whose in vivo functions remain elusive. In this study, we performed gain-of-function and loss-of-function analysis in Drosophila and identified flfl as a negative regulator of JNK pathway-mediated cell death. While ectopic expression of flfl suppresses TNF-triggered JNK-dependent cell death, loss of flfl promotes JNK activation and cell death in the developing eye and wing. These data report for the first time an essential physiological function of flfl in maintaining tissue homeostasis and organ development. As the JNK signaling pathway has been evolutionary conserved from fly to human, a similar role of PP4R3 in JNK-mediated physiological process is speculated.

No MeSH data available.


Related in: MedlinePlus