Biological Activity of Natural Cleavage Products of Slit in the Developing Drosophila Heart Biological Activity of Natural Cleavage Products of Slit in the Developing Drosophila Heart By

iii The Slit morphogen is a secreted glycoprotein that is naturally cleaved into two fragments. The amino fragment (N-Slit) contains Leucine Rich Repeats (LRR) that are recognised by Robo receptors, and is sufficient to mediate attractive or repellent signalling in Drosophila tissues, for example, during growth cone guidance at the midline of the nervous system. The carboxy fragment (C-Slit) is composed of EGF repeats and a Laminin-like globular domain. Although C-Slit expression does not restore repellent signalling, it does rescue other morphogenetic defects in slit mutants. Formation of the dorsal vessel (or heart) requires function of slit and robo. Slit is required for coordinated migration of heart cell precursors, cell polarisation and the formation of a lumen in the heart tube. We have characterised the morphogenetic activities of N- Slit and C-Slit during assembly of the heart. Our laboratory has shown that Slit transgenes lacking the LRR region fail to rescue the mutant phenotype in the nervous system. However, slit trangenes lacking the LR