TY - JOUR
T1 - The role of the Drosophila TAK homologue dTAK during development
AU - Mihaly, Jozsef
AU - Kockel, Lutz
AU - Gaengel, Konstantin
AU - Weber, Ursula
AU - Bohmann, Dirk
AU - Mlodzik, Marek
N1 - Funding Information:
We thank David Schneider, Beth Stronach and Norbert Perrimon for sharing unpublished results. We are grateful to Ann-Mari Voie for generating transgenic fly strains, Anna Cyrklaff for chromosome in situ hybridizations and Chris Blaumueller for instructions on Acridine Orange staining protocols. We thank K. Basler, S. Cohen, N. Perrimon, G. Rubin, H. Steller and the Bloomington Stock Center for fly strains and reagents, J. Curtiss for comments on the manuscript, and members of the Mlodzik and Bohmann labs for helpful discussions. L.K. is grateful to H. Steller for allowing him to complete experiments in his lab. J.M. was supported by an EMBO long-term fellowship.
PY - 2001
Y1 - 2001
N2 - The TAK kinases belong to the MAPKKK group and have been implicated in a variety of signaling events. Originally described as a TGF-β activated kinase (TAK) it has, however, subsequently been demonstrated to signal through p38, Jun N-terminal kinase (JNK) and Nemo types of MAP kinases, and the NFκB inducing kinase. Despite these multiple proposed functions, the in vivo role of TAK family kinases remains unclear. Here we report the isolation and genetic characterization of the Drosophila TAK homologue (dTAK). By employing overexpression and double-stranded RNA interference (RNAi) techniques we have analyzed its function during embryogenesis and larval development. Overexpression of dTAK in the embryonic epidermis is sufficient to induce the transcription of the JNK target genes decapentaplegic and puckered. Furthermore, overexpression of dominant negative (DN) or wild-type forms of dTAK in wing and eye imaginal discs, respectively, results in defects in thorax closure and ommatidial planar polarity, two well described phenotypes associated with JNK signaling activity. Surprisingly, RNAi and DN-dTAK expression studies in the embryo argue for a differential requirement of dTAK during developmental processes controlled by JNK signaling, and a redundant or minor role of dTAK in dorsal closure. In addition, dTAK-mediated activation of JNK in the Drosophila eye imaginal disc leads to an eye ablation phenotype due to ectopically induced apoptotic cell death. Genetic analyses in the eye indicate that dTAK can also act through the p38 and Nemo kinases in imaginal discs. Our results suggest that dTAK can act as a JNKKK upstream of JNK in multiple contexts and also other MAPKs in the eye. However, the loss-of-function RNAi studies indicate that it is not strictly required and thus either redundant or playing only a minor role in the context of embryonic dorsal closure.
AB - The TAK kinases belong to the MAPKKK group and have been implicated in a variety of signaling events. Originally described as a TGF-β activated kinase (TAK) it has, however, subsequently been demonstrated to signal through p38, Jun N-terminal kinase (JNK) and Nemo types of MAP kinases, and the NFκB inducing kinase. Despite these multiple proposed functions, the in vivo role of TAK family kinases remains unclear. Here we report the isolation and genetic characterization of the Drosophila TAK homologue (dTAK). By employing overexpression and double-stranded RNA interference (RNAi) techniques we have analyzed its function during embryogenesis and larval development. Overexpression of dTAK in the embryonic epidermis is sufficient to induce the transcription of the JNK target genes decapentaplegic and puckered. Furthermore, overexpression of dominant negative (DN) or wild-type forms of dTAK in wing and eye imaginal discs, respectively, results in defects in thorax closure and ommatidial planar polarity, two well described phenotypes associated with JNK signaling activity. Surprisingly, RNAi and DN-dTAK expression studies in the embryo argue for a differential requirement of dTAK during developmental processes controlled by JNK signaling, and a redundant or minor role of dTAK in dorsal closure. In addition, dTAK-mediated activation of JNK in the Drosophila eye imaginal disc leads to an eye ablation phenotype due to ectopically induced apoptotic cell death. Genetic analyses in the eye indicate that dTAK can also act through the p38 and Nemo kinases in imaginal discs. Our results suggest that dTAK can act as a JNKKK upstream of JNK in multiple contexts and also other MAPKs in the eye. However, the loss-of-function RNAi studies indicate that it is not strictly required and thus either redundant or playing only a minor role in the context of embryonic dorsal closure.
KW - Apoptosis
KW - Dorsal closure
KW - Drosophila
KW - Jun N-terminal kinase
KW - MAPK signaling
KW - Planar polarity
UR - http://www.scopus.com/inward/record.url?scp=0035060798&partnerID=8YFLogxK
U2 - 10.1016/S0925-4773(01)00285-4
DO - 10.1016/S0925-4773(01)00285-4
M3 - Article
C2 - 11287182
AN - SCOPUS:0035060798
SN - 0925-4773
VL - 102
SP - 67
EP - 79
JO - Mechanisms of Development
JF - Mechanisms of Development
IS - 1-2
ER -