lobula cells. Variable expression of Robo receptors on Drosophila olfactory neurons controls axonal organization in the olfactory lobes. In vertebrates, Slit1 plays an important role in vomeronasal organ (VNO) axonal targeting to the accessory olfactory bulb (AOB). In 2009, a combination of Slit-Robo and Netrin-Frazzled signaling in Drosophila was shown to govern the establishment of myotopic maps, which describe the innervation of motorneuron dendrites in the muscle field. Cell migration Slit-Robo has been shown to influence the migration of neurons and glia, leukocytes, and endothelial cells. Slit1 and Slit2 mediate the repulsive activity of the septum and choroid plexus which orient the migration of undifferentiated cells of the subventricular zone (SVZ) on the rostral migratory stream (RMS) to the olfactory bulb, where they differentiate into olfactory neurons. The contribution of Robo signaling in this system is unclear, but it is known that migrating neuroblasts do express Robo2 and Robo3 mRNAs. During the developmental of mouse peripheral auditory system, Slit/Robo signaling imposes a restriction force on spiral ganglia neurons to ensure their precise positioning for correct spiral ganglia-cochlear hair cells innervations. Implications in disease Cancer and vascular disease Inhibition of Robo1, which colocalizes with von Willebrand factor in tumor endothelial cells, leads to reduced micro-vessel density and tumor mass of malignant melanoma. Slit2 is known to mediate this effect. Robo4, also known as magic roundabout, is an endothelial specific Robo which, upon binding Slit2, blocks Src family kinase activation, thereby inhibiting VEGF-165-induced migration and permeability in vitro and vascular leak in vivo. This suggests that combined VEGF/Slit2 therapies could be useful in preventing tumor angiogenesis and vascular leak or edema after heart attack or stroke. Horizontal gaze palsy with progressive scoliosis The homozygous Robo3 mutations have been associated with typical ophthalmologic horizontal gaze palsy with progressive scoliosis, which is characterized by oculomotor problems and general disturbances in innervation. Dyslexia Robo1 has been implicated as one of 14 different candidate genes for dyslexia, and one of 10 that fit into a theoretical molecular network involved in neuronal migration and neurite outgrowth. Slit2 is predicted to play a role in the network. References Further reading Cell signaling Developmental neuroscience Slit proteins