The creation of complex neuronal networks relies on ligand-receptor interactions 
that mediate attraction or repulsion towards specific targets. Roundabouts 
comprise a family of single-pass transmembrane receptors facilitating this 
process upon interaction with the soluble extracellular ligand Slit protein 
family emanating from the midline. Due to the complexity and flexible nature of 
Robo receptors , their overall structure has remained elusive until now. Recent 
structural studies of the Robo 1 and Robo 2 ectodomains have provided the basis 
for a better understanding of their signalling mechanism. These structures 
reveal how Robo receptors adopt an auto-inhibited conformation on the cell 
surface that can be further stabilised by cis and/or trans oligmerisation 
arrays. Upon Slit -N binding Robo receptors must undergo a conformational change 
for Ig4 mediated dimerisation and signaling, probably via endocytosis. 
Furthermore, it's become clear that Robo receptors do not only act alone, but as 
large and more complex cell surface receptor assemblies to manifest directional 
and growth effects in a concerted fashion. These context dependent assemblies 
provide a mechanism to fine tune attractive and repulsive signals in a 
combinatorial manner required during neuronal development. While a mechanistic 
understanding of Slit mediated Robo signaling has advanced significantly further 
structural studies on larger assemblies are required for the design of new 
experiments to elucidate their role in cell surface receptor complexes. These 
will be necessary to understand the role of Slit -Robo signaling in 
neurogenesis, angiogenesis, organ development and cancer progression. In this 
chapter, we provide a review of the current knowledge in the field with a 
particular focus on the Roundabout receptor family.