A Systematic Analysis of Tinman Function Reveals Eya and JAK-STAT Signaling as Essential Regulators of Muscle Development

Summary 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.