The Slit-Robo signalling pathway and congenital heart disease
Mathilda Mommersteeg
Department of Physiology, Anatomy and Genetics, University of Oxford
The Roundabout (Robo) transmembrane receptors and their Slit ligands, initially identified in
Drosophila, became known for their roles in axonal guidance in the embryonic nervous
system. However, since this discovery, many new roles for the Slit-Robo signalling pathway
have been identified, mainly in cancer and embryonic development. In Drosophila and
zebrafish, Slit-Robo signalling plays key roles in cell adhesion during cardiac cell
polarisation, morphogenesis, migration and lumen formation. However, knowledge of the
pathway during mammalian heart development is limited. We have now identified a broad
spectrum of cardiac defects in mouse mutants for Robo and Slit, ranging from membranous
ventricular septum defects to bicuspid aortic valves and congenital absence of the
pericardium. The different Slit ligands and Robo receptors have unique functions during
development of specific heart regions and the Slit-Robo signalling pathway likely enforces its
role by regulating Notch signalling, making these mutants a valuable new model to study the
molecular mechanisms underlying congenital heart disease.
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