Attractive and repulsive receptors regulate cell motility and attachment in axon guidance, vascular growth, immune cell regulation and tumor progression. There is strong evidence that development of the nervous and vascular systems is controlled by common cues.

Semaphorins, Ephrins, SLITs and Netrins are the four major guidance factors. Their cognate receptors are Plexins and Neuropilins, Ephs, ROBOs, UNC5 and DCC.

SLITs belong to repulsive cues. Intracellular molecular mechanisms leading to repulsive responses involve cytoskeletal reorganization.

Small GTPases play important role in this signaling {15818466}. SLIT proteins guide neuronal and leukocyte migration through transmembrane receptors Roundabout (ROBO). ROBO1 interacts with a family of Rho GTPase activating proteins (GAPs). SRGAP1 is expressed in regions responsive to SLIT. SLIT enhances SRGAP1 / ROBO1 interaction and inactivates CDC42 which leads to inhibition of actin polymerization, cell repulsive response and neuronal migration [1].

Another signaling pathway that guidance signals to the regulation of cytoskeletal dynamics is the c-Abl protein kinase pathway. This pathway mediates signals downstream of the multiple ROBO receptors [2].

1. Wong K, Ren XR, Huang YZ, Xie Y, Liu G, Saito H, Tang H, Wen L, Brady-Kalnay SM, Mei L, Wu JY, Xiong WC, Rao Y
   Signal transduction in neuronal migration: roles of GTPase activating proteins and the small GTPase Cdc42 in the Slit-Robo pathway. Cell 2001 Oct 19;107(2):209-21
2. Wills Z, Emerson M, Rusch J, Bikoff J, Baum B, Perrimon N, Van Vactor D
   A Drosophila homolog of cyclase-associated proteins collaborates with the Abl tyrosine kinase to control midline axon pathfinding. Neuron 2002 Nov 14;36(4):611-22