During vertebrate heart development, myocardial and endocardial precursors migrate towards the embryonic midline where they fuse into a linear heart tube. Now, Jason Fish, Stephanie Woo and colleagues report that a Slit/miR-218/Robo signalling pathway regulates heart tube assembly in zebrafish (see p. ). Members of the Slit family of secreted ligands interact with Roundabout (Robo) receptors to provide guidance cues during the development of several organs; development is also regulated by microRNAs (miRNAs) that can fine-tune the expression of developmentally important genes. The researchers show that the conserved miRNA miR-218 is intronically encoded in slit2 and slit3, and that it suppresses Robo1 and Robo2 expression. Further analyses indicate that Slit2, Robo1 and miR-218 are required for the formation of the zebrafish heart tube and that these factors act, in part, by modulating Vegf signalling. These findings reveal a novel signalling pathway for vertebrate heart tube formation and suggest a new paradigm of receptor/ligand regulation in which a ligand-encoded microRNA regulates the expression of its own receptor.
