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BioMed Research International
Volume 2014 (2014), Article ID 683025, 9 pages
Review Article

Role of ROBO4 Signalling in Developmental and Pathological Angiogenesis

Cancer Genetics Laboratory, Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi 221 005, India

Received 25 April 2013; Revised 29 November 2013; Accepted 12 December 2013; Published 6 February 2014

Academic Editor: Manoor Prakash Hande

Copyright © 2014 Suresh Singh Yadav and Gopeshwar Narayan. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Transmembrane roundabout receptor family members (ROBO1–ROBO4) principally orchestrate the neuronal guidance mechanism of the nervous system. Secreted glycoprotein SLITs are the most appreciated ligands for ROBOs. Recently identified ROBO4 is the key mediator of SLIT-ROBO mediated developmental and pathological angiogenesis. Although SLIT2 has been shown to interact with ROBO4 as ligand, it remains an open question whether this protein is the physiologic partner of ROBO4. The purpose of this review is to summarise how reliable SLIT2 as ligand for ROBO4 is, if not what the other possible mechanisms demonstrated till date for ROBO4 mediated developmental and pathological angiogenesis are. We conclude that ROBO4 is expressed specially in vascular endothelial cells and maintains the vascular integrity via either SLIT2 dependent or SLIT2 independent manner. On the contrary, it promotes the pathological angiogenesis by involving different signalling arm(s)/unknown ligand(s). This review explores the interactions SLIT2/ROBO1, SLIT2/ROBO1–ROBO4, ROBO1/ROBO4, and ROBO4/UNC5B which can be promising and potential therapeutic targets for developmental angiogenesis defects and pathological angiogenesis. Finally we have reviewed the ROBO4 signalling pathways and made an effort to elaborate the insight of this signalling as therapeutic target of pathological angiogenesis.