Regulation of morphogen signaling at the plasma membrane: Novel components and interactions in the formation of graded BMP signaling in Drosophila wing imaginal discs

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Organ growth and patterning by gradients of secreted signaling molecules, so-called morphogens, is a fundamental principle in animal development. Over the last two decades, the wing imaginal disc of Drosophila, the larval precursor of the wing, has emerged as a particularly important paradigm for studying properties and functions of morphogen signaling. In this tissue, the ligand Decapentaplegic (Dpp; a drosophila ligand of the BMP superfamily) orchestrates long-range, graded BMP signaling along the anterior-posterior axis to equip cells of the epithelium with positional information. Relatively little is known about the molecular mechanisms that establish and maintain proper morphogen signal-ing. Our recent work in this system culminated in the identification of the secreted protein Pentagone (Pent) that, together with glypicans, regulates the shape of the BMP signaling gradient. In subsequent studies we have identified two hitherto uncharacterized transmembrane proteins that might work in concert with Pent and glypicans in the regulation of BMP morphogen by regulating ligand distribution and ligand-receptor interactions. Altogether, the findings suggest the existence of a complex network of proteins that regulate morphogen signaling at the plasma membrane. The proposed research aims at identifying additional components of the network and understanding its molecular function in the regulation of morphogen signaling.