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.
Liu
Ya-Hsin
YH
European Molecular Biology Laboratory, Heidelberg, Germany.
Jakobsen
Janus S
JS
Valentin
Guillaume
G
Amarantos
Ioannis
I
Gilmour
Darren T
DT
Furlong
Eileen E M
EE
D000818:Animals; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster; D005136:Eye Proteins / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D053613:Janus Kinase 1 / Q000378:metabolism*; D008954:Models, Biological; D024510:Muscle Development; D009132:Muscles / Q000378:metabolism*; D010641:Phenotype; D012097:Repressor Proteins / Q000378:metabolism*; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism*; D014158:Transcription, Genetic; D019076:Transgenes; D015027:Zebrafish
D029721:Drosophila Proteins; D005136:Eye Proteins; D012097:Repressor Proteins; D050794:STAT1 Transcription Factor; D015534:Trans-Activators; C092694:eya protein, Drosophila; C102933:tin protein, Drosophila; D053613:Janus Kinase 1