Slit2 signaling through Robo1 and Robo2 is required for retinal neovascularization

Nature Medicine

Volumn 21, Issue 5, 2015, Pages 483-491

  Rama, Nicolas ^a,b,c   Dubrac, Alexandre ^d   Mathivet, Thomas ^e   Ní Chárthaigh, Róisín Ana ^a,b,c   Genet, Gael ^d   Cristofaro, Brunella ^e   Pibouin Fragner, Laurence ^e   Ma, Le ^f   Eichmann, Anne ^d,e   Chédotal, Alain ^a,b,c  

^a INSTITUT DE LA VISION   (France)

^b SORBONNE UNIVERSITÉ   (France)

^c CNRS   (France)

^d YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^e PSL RESEARCH UNIVERSITY   (France)

^f THOMAS JEFFERSON UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

PROTEIN DERIVATIVE; PROTEIN ROBO1; PROTEIN ROBO2; RAC1 PROTEIN; ROUNDABOUT RECEPTOR; SLIT2 PROTEIN; UNCLASSIFIED DRUG; IMMUNOGLOBULIN RECEPTOR; MESSENGER RNA; NERVE PROTEIN; ROBO2 PROTEIN, HUMAN; ROBO2 PROTEIN, MOUSE; SIGNAL PEPTIDE; SLIT HOMOLOG 2 PROTEIN; VASCULOTROPIN A;

ANGIOGENESIS; ANIMAL CELL; ARTICLE; CELL ACTIVATION; CELL MIGRATION; CONTROLLED STUDY; ENDOTHELIUM CELL; HUMAN; HUMAN CELL; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; RETINA NEOVASCULARIZATION; SIGNAL TRANSDUCTION; ANIMAL; APOPTOSIS; C57BL MOUSE; CELL MOTION; CELL PROLIFERATION; CYTOLOGY; DISEASE MODEL; DRUG EFFECTS; EMBRYOLOGY; GENE EXPRESSION REGULATION; GENETICS; KNOCKOUT MOUSE; LUNG; MALE; METABOLISM; MOUSE; NEOVASCULARIZATION (PATHOLOGY); RETINA; UMBILICAL VEIN ENDOTHELIAL CELL;

ANIMALS; APOPTOSIS; CELL MOVEMENT; CELL PROLIFERATION; DISEASE MODELS, ANIMAL; ENDOTHELIAL CELLS; GENE EXPRESSION REGULATION, DEVELOPMENTAL; HUMAN UMBILICAL VEIN ENDOTHELIAL CELLS; HUMANS; INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS; LUNG; MALE; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; NEOVASCULARIZATION, PATHOLOGIC; NERVE TISSUE PROTEINS; RECEPTORS, IMMUNOLOGIC; RETINA; RETINAL NEOVASCULARIZATION; RNA, MESSENGER; SIGNAL TRANSDUCTION; VASCULAR ENDOTHELIAL GROWTH FACTOR A;

EID: 84937758440     PISSN: 10788956     EISSN: 1546170X     Source Type: Journal    
DOI: 10.1038/nm.3849     Document Type: Article

References (52)

1. Ferrara, N. Vascular endothelial growth factor and age-related macular degeneration: from basic science to therapy. Nat. Med. 16, 1107-1111 (2010).
2. Miller, J.W., Le Couter, J., Strauss, E.C. & Ferrara, N. Vascular endothelial growth factor a in intraocular vascular disease. Ophthalmology 120, 106-114 (2013).
3. Lim, L.S., Mitchell, P., Seddon, J.M., Holz, F.G. & Wong, T.Y. Age-related macular degeneration. Lancet 379, 1728-1738 (2012).
4. Brose, K. et al. Slit proteins bind Robo receptors and have an evolutionarily conserved role in repulsive axon guidance. Cell 96, 795-806 (1999).
5. Kidd, T., Bland, K.S. & Goodman, C.S. Slit is the midline repellent for the robo receptor in Drosophila. Cell 96, 785-794 (1999).
6. Ypsilanti, A.R., Zagar, Y. & Chedotal, A. Moving away from the midline: new developments for Slit and Robo. Development 137, 1939-1952 (2010).
7. Koch, A.W. et al. Robo4 maintains vessel integrity and inhibits angiogenesis by interacting with UNC5B. Dev. Cell 20, 33-46 (2011).
8. Zelina, P. et al. Signaling switch of the axon guidance receptor Robo3 during vertebrate evolution. Neuron 84, 1258-1272 (2014).
9. Jones, C.A. et al. Robo4 stabilizes the vascular network by inhibiting pathologic angiogenesis and endothelial hyperpermeability. Nat. Med. 14, 448-453 (2008).
10. Jones, C.A. et al. Slit2-Robo4 signalling promotes vascular stability by blocking Arf6 activity. Nat. Cell Biol. 11, 1325-1331 (2009).
11. Huang, L. et al. Expression of Robo4 in the fibrovascular membranes from patients with proliferative diabetic retinopathy and its role in RF/6A and RPE cells. Mol. Vis. 15, 1057-1069 (2009).
12. Zhou, W. et al. The role of SLIT-ROBO signaling in proliferative diabetic retinopathy and retinal pigment epithelial cells. Mol. Vis. 17, 1526-1536 (2011).
13. Zhang, B. et al. Repulsive axon guidance molecule Slit3 is a novel angiogenic factor. Blood 114, 4300-4309 (2009).
14. Yang, X.M. et al. Slit-Robo signaling mediates lymphangiogenesis and promotes tumor lymphatic metastasis. Biochem. Biophys. Res. Commun. 396, 571-577 (2010).
15. Urbich, C. et al. HDAC5 is a repressor of angiogenesis and determines the angiogenic gene expression pattern of endothelial cells. Blood 113, 5669-5679 (2009).
16. Kaur, S. et al. Robo4 signaling in endothelial cells implies attraction guidance mechanisms. J. Biol. Chem. 281, 11347-11356 (2006).
17. Plump, A.S. et al. Slit1 and Slit2 cooperate to prevent premature midline crossing of retinal axons in the mouse visual system. Neuron 33, 219-232 (2002).
18. Fouquet, C. et al. Robo1 and Robo2 control the development of the lateral olfactory tract. J. Neurosci. 27, 3037-3045 (2007).
19. Morlot, C. et al. Structural insights into the Slit-Robo complex. Proc. Natl. Acad. Sci. USA 104, 14923-14928 (2007).
20. Guo, C., Yang, W. & Lobe, C.G. A Cre recombinase transgene with mosaic, widespread tamoxifen-inducible action. Genesis 32, 8-18 (2002).
21. Birdsey, G.M. et al. Transcription factor Erg regulates angiogenesis and endothelial apoptosis through VE-cadherin. Blood 111, 3498-3506 (2008).
22. Guijarro-Muñoz, I. et al. The axonal repellent Slit2 inhibits pericyte migration: potential implications in angiogenesis. Exp. Cell Res. 318, 371-378 (2012).
23. Sörensen, I., Adams, R.H. & Gossler, A. DLL1-mediated Notch activation regulates endothelial identity in mouse fetal arteries. Blood 113, 5680-5688 (2009).
24. Yoshioka, K. et al. Endothelial PI3K-C2α, a class II PI3K, has an essential role in angiogenesis and vascular barrier function. Nat. Med. 18, 1560-1569 (2012).
25. del Toro, R. et al. Identification and functional analysis of endothelial tip cell-enriched genes. Blood 116, 4025-4033 (2010).
26. Wang, B. et al. Induction of tumor angiogenesis by Slit-Robo signaling and inhibition of cancer growth by blocking Robo activity. Cancer Cell 4, 19-29 (2003).
27. Grieshammer, U. et al. SLIT2-mediated ROBO2 signaling restricts kidney induction to a single site. Dev. Cell 6, 709-717 (2004).
28. Lu, W. et al. Disruption of ROBO2 is associated with urinary tract anomalies and confers risk of vesicoureteral reflux. Am. J. Hum. Genet. 80, 616-632 (2007).
29. Long, H. et al. Conserved roles for Slit and Robo proteins in midline commissural axon guidance. Neuron 42, 213-223 (2004).
30. Liu, D. et al. Neuronal chemorepellent Slit2 inhibits vascular smooth muscle cell migration by suppressing small GTPase Rac1 activation. Circ. Res. 98, 480-489 (2006).
31. Wang, Y. et al. Norrin/Frizzled4 signaling in retinal vascular development and blood brain barrier plasticity. Cell 151, 1332-1344 (2012).
32. Adams, R.H. & Eichmann, A. Axon guidance molecules in vascular patterning. Cold Spring Harb. Perspect. Biol. 2, a001875 (2010).
33. Maisonpierre, P.C. et al. Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science 277, 55-60 (1997).
34. Lu, X. et al. The netrin receptor UNC5B mediates guidance events controlling morphogenesis of the vascular system. Nature 432, 179-186 (2004).
35. Ridgway, J. et al. Inhibition of Dll4 signalling inhibits tumour growth by deregulating angiogenesis. Nature 444, 1083-1087 (2006).
36. Hellström, M. et al. Dll4 signalling through Notch1 regulates formation of tip cells during angiogenesis. Nature 445, 776-780 (2007).
37. Larrivée, B. et al. ALK1 signaling inhibits angiogenesis by cooperating with the Notch pathway. Dev. Cell 22, 489-500 (2012).
38. Small, E.M., Sutherland, L.B., Rajagopalan, K.N., Wang, S. & Olson, E.N. MicroRNA-218 regulates vascular patterning by modulation of Slit-Robo signaling. Circ. Res. 107, 1336-1344 (2010).
39. Fish, J.E. et al. A Slit/miR-218/Robo regulatory loop is required during heart tube formation in zebrafish. Development 138, 1409-1419 (2011).
40. Ridley, A.J. et al. Cell migration: integrating signals from front to back. Science 302, 1704-1709 (2003).
41. Connor, K.M. et al. Quantification of oxygen-induced retinopathy in the mouse: a model of vessel loss, vessel regrowth and pathological angiogenesis. Nat. Protoc. 4, 1565-1573 (2009).
42. Mehlen, P., Delloye-Bourgeois, C. & Chedotal, A. Novel roles for Slits and netrins: axon guidance cues as anticancer targets? Nat. Rev. Cancer 11, 188-197 (2011).
43. Benedito, R. et al. Notch-dependent VEGFR3 upregulation allows angiogenesis without VEGF-VEGFR2 signalling. Nature 484, 110-114 (2012).
44. Germain, S., Monnot, C., Muller, L. & Eichmann, A. Hypoxia-driven angiogenesis: role of tip cells and extracellular matrix scaffolding. Curr. Opin. Hematol. 17, 245-251 (2010).
45. Domyan, E.T. et al. Roundabout receptors are critical for foregut separation from the body wall. Dev. Cell 24, 52-63 (2013).
46. Marillat, V. et al. Spatiotemporal expression patterns of slit and robo genes in the rat brain. J. Comp. Neurol. 442, 130-155 (2002).
47. Nguyen-Ba-Charvet, K.T. et al. Multiple roles for slits in the control of cell migration in the rostral migratory stream. J. Neurosci. 24, 1497-1506 (2004).
48. Di Meglio, T. Nguyen-Ba-Charvet, K.T., Tessier-Lavigne, M., Sotelo, C. & Chédotal, A. Molecular mechanisms controlling midline crossing by precerebellar neurons. J. Neurosci. 28, 6285-6294 (2008).
49. Chauvet, S. et al. Gating of Sema3E/PlexinD1 signaling by neuropilin-1 switches axonal repulsion to attraction during brain development. Neuron 56, 807-822 (2007).
50. Xu, Y. et al. Neuropilin-2 mediates VEGF-C-induced lymphatic sprouting together with VEGFR3. J. Cell Biol. 188, 115-130 (2010).
51. Jones, E.A., Yuan, L., Breant, C., Watts, R.J. & Eichmann, A. Separating genetic and hemodynamic defects in neuropilin 1 knockout embryos. Development 135, 2479-2488 (2008).
52. Lanahan, A. et al. The neuropilin 1 cytoplasmic domain is required for VEGF-A-dependent arteriogenesis. Dev. Cell 25, 156-168 (2013).