| Graded outputs of several signaling pathways have been shown to provide positional information for the specification of multiple cell fates in a correct spatial organization, a process critical for the proper functioning of tissues and organs of multicellular organisms. These activity gradients are proposed to form in response to long range functions of signaling molecules that are secreted from localized sources and distributed across tissues in concentration gradients. Coordinate actions of multiple ligands with distinct requirements for patterning are often required for the proper specification of all the cell fates within a developing cellular field. How do multiple ligands cooperate to establish an activity gradient? How are the different effects of each ligand mediated? Several factors, including secreted ligand antagonists and agonists, Extracellular Matrix (ECM) components and receptors interact with these secreted ligands and influence both their distribution and signaling activity. Differential interactions with these factors are likely to be important determinants of the extent of each individual ligand's contribution to overall patterning. We have attempted to address some of these questions using the BMP activity gradient that forms in the Drosophila wing imaginal disc as our model system. Two BMP ligands, encoded by the decapentaplegic (dpp) and glass bottom boat ( gbb) genes are required for full patterning in this tissue and two type I receptors, encoded by the saxophone (sax) and thickveins (tkv) genes are proposed to mediate effects of Gbb and Dpp. However, how these BMP signaling components cooperate to form a BMP activity gradient is not clear. Our detailed genetic analysis of the function of these genes in patterning revealed (1) the BMP activity gradient in the wing disc is established by long range Gbb signaling and short range Dpp signaling both of which require Tkv function, and (2) the other type I receptor Sax primarily functions to restrict the range of the activity gradient by sequestering Gbb. Both the range difference between Gbb and Dpp and the novel antagonistic function of Sax are two previously unappreciated aspects of gradient formation and signaling and they provide a novel paradigm for gradient function and BMP signaling. |
