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

Abstract

<p>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 <em>Drosophila </em>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 <em>slit</em> mutants.</p> <p>Formation of the dorsal vessel (or heart) requires function of <em>slit</em> and <em>robo</em>. 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.</p> <p>Our laboratory has shown that Slit transgenes lacking the LRR region fail to rescue the mutant phenotype in the nervous system. However, <em>slit</em> trangenes lacking the LRR results in a partial rescue phenotype in the heart suggesting that C-Slit might have functional significance in the heart. Therefore, Slit function in heart vasculogenesis has different requirements compared to the nervous system. For example, Slit –Robo2 interaction may have an adhesive function in addition to a signalling function during vasculogenesis.</p> <p>Our results indicate that C-Slit funtions as a heart morphogen. In <em>slit</em> mutants, over-expression of C-Slit results in a partial rescue phenotype with several features such as cell clumping, overlapping of cells and cells which are elongated. Together, these data suggest alternative functions for Slit during heart morphogenesis.</p>