A Systematic Analysis of Tinman Function Reveals Eya and JAK-STAT Signaling as Essential Regulators of Muscle Development
pmid: 19217429
A Systematic Analysis of Tinman Function Reveals Eya and JAK-STAT Signaling as Essential Regulators of Muscle Development
Nk-2 proteins are essential developmental regulators from flies to humans. In Drosophila, the family member tinman is the major regulator of cell fate within the dorsal mesoderm, including heart, visceral, and dorsal somatic muscle. To decipher Tinman's direct regulatory role, we performed a time course of ChIP-on-chip experiments, revealing a more prominent role in somatic muscle specification than previously anticipated. Through the combination of transgenic enhancer-reporter assays, colocalization studies, and phenotypic analyses, we uncovered two additional factors within this myogenic network: by activating eyes absent, Tinman's regulatory network extends beyond developmental stages and tissues where it is expressed; by regulating stat92E expression, Tinman modulates the transcriptional readout of JAK/STAT signaling. We show that this pathway is essential for somatic muscle development in Drosophila and for myotome morphogenesis in zebrafish. Taken together, these data uncover a conserved requirement for JAK/STAT signaling and an important component of the transcriptional network driving myogenesis.
- University of Zurich Switzerland
- University of Copenhagen Denmark
- University of Copenhagen Denmark
- European Molecular Biology Laboratory Germany
Transcription, Genetic, DEVBIO, Muscle Development, Models, Biological, 1309 Developmental Biology, 1307 Cell Biology, 1300 General Biochemistry, Genetics and Molecular Biology, 1312 Molecular Biology, Animals, Drosophila Proteins, Transgenes, Eye Proteins, Zebrafish, Muscles, Gene Expression Regulation, Developmental, Janus Kinase 1, 10124 Institute of Molecular Life Sciences, Repressor Proteins, Drosophila melanogaster, Phenotype, STAT1 Transcription Factor, Trans-Activators, 570 Life sciences; biology, Developmental Biology, Signal Transduction
Transcription, Genetic, DEVBIO, Muscle Development, Models, Biological, 1309 Developmental Biology, 1307 Cell Biology, 1300 General Biochemistry, Genetics and Molecular Biology, 1312 Molecular Biology, Animals, Drosophila Proteins, Transgenes, Eye Proteins, Zebrafish, Muscles, Gene Expression Regulation, Developmental, Janus Kinase 1, 10124 Institute of Molecular Life Sciences, Repressor Proteins, Drosophila melanogaster, Phenotype, STAT1 Transcription Factor, Trans-Activators, 570 Life sciences; biology, Developmental Biology, Signal Transduction
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