In mammals, the JAK/STAT (Janus Kinase/Signal Transducer and Activator of Transcription) signaling pathway is activated in response to cytokines and growth factors to control blood cell development, proliferation and cell determination. In Drosophila, a conserved JAK/STAT signaling pathway controls segmentation in embryos, as well as blood cell development and other processes in larvae and adults. During embryogenesis, transduction of the Unpaired [Upd; also known as Outstretched (Os)] ligand through the JAK/STAT pathway requires Domeless, a putative membrane protein with distant homology to vertebrate type I cytokine receptors. We have isolated domeless(dome) in a screen to identify genes essential in epithelial morphogenesis during oogenesis. The level of dome activity is critical for proper border cell migration and is controlled in part through a negative feedback loop. In addition to its essential role in border cells, we show that dome is required in the germarium for the polarization of follicle cells during encapsulation of germline cells. In this process,dome controls the expression of the apical determinant Crumbs. In contrast to the ligand Upd, whose expression is limited to a pair of polar cells at both ends of the egg chamber, dome is expressed in all germline and follicle cells. However, the Dome protein is specifically localized at apicolateral membranes and undergoes ligand-dependent internalization in the follicle cells. dome mutations interact genetically with JAK/STAT pathway genes in border cell migration and abolish the nuclear translocation of Stat92E in vivo. We also show that domefunctions downstream of upd and that both the extracellular and intracellular domains of Dome are required for JAK/STAT signaling. Altogether,our data indicate that Dome is an essential receptor molecule for Upd and JAK/STAT signaling during oogenesis.

Emergence of asymmetry from an initially symmetrical state is a universal transition in Nature. Living organisms show striking asymmetries at the molecular, cellular, tissular and organismal level. However, whether and how multilevel asymmetries are related remains unclear. Here, we show that Drosophila Myosin 1D (Myo1D) and Myosin 1C (Myo1C) are sufficient to generate de novo directional twisting of cells, single organs or the whole body in opposite directions. We show that directionality lies in the Myosins’ motor domain and is swappable, and that Myo1D powers gliding of actin filaments in circular, counterclockwise paths in vitro. Altogether, our results reveal the molecular motor Myo1D as a chiral determinant, sufficient to break symmetry at all biological scales through chiral interaction with the actin cytoskeleton.