Notch-mediated segmentation and growth control of the Drosophila leg

The possession of segmented appendages is a defining characteristic of the arthropods. By analyzing both loss-of-function and ectopic expression exper iments, we show that the Notch signaling pathway plays a fundamental role i n the segmentation and growth of the Drosophila leg. Local activation of No tch is necessary and sufficient to promote the formation of joints between segments. This segmentation process requires the participation of the Notch ligands, Serrate and Delta, as well as fringe. These three proteins are ea ch expressed in the developing leg and antennal imaginal discs in a segment ally repeated pattern that is regulated downstream of the action of Wingles s and Decapentaplegic. Our studies further show that Notch activation is bo th necessary and sufficient to promote leg growth. We also identify target genes regulated both positively and negatively downstream of Notch signalin g that are required for normal leg development. Together, these observation s outline a regulatory hierarchy for the segmentation and growth of the leg . The Notch pathway is also deployed for segmentation during vertebrate som itogenesis, which raises the possibility of a common origin for the segment ation of these distinct tissues. (C) 1999 Academic Press.