Robo4 and VEGF signaling pathways crosstalk (WP3864)

Mus musculus

This pathway is based on Figure 2 of "Robo4: a guidance receptor that regulates angiogenesis." ( The gene Robo4 plays a role in regulating vascular stability in mice. Robo4 inhibits the gene Notch1, which regulates tip cell formation, in order to create more tip cells. Robo4 also inhibits cell migration, decreasing vessel complexity. The combination of Slit2 and Robo4 inhibits the activation of Src by VEGF-165 and VEGFR2. This inhibition reduces vascular leakage of Evans Blue from retinal blood vessels. More experimentation is necessary to determine whether Robo4 will inhibit other members of the Src family.


AAR&Co , Martina Summer-Kutmon , Kristina Hanspers , and Eric Weitz


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Mus musculus



Pathway Ontology

Notch signaling pathway regulatory pathway


Label Type Compact URI Comment
Robo4 GeneProduct ensembl:ENSMUSG00000032125
Slit2 GeneProduct ensembl:ENSMUSG00000031558
VEGFR2 GeneProduct ensembl:ENSMUSG00000062960
Rac1 GeneProduct ensembl:ENSMUSG00000001847
Vegfa GeneProduct ensembl:ENSMUSG00000023951
Src GeneProduct ensembl:ENSMUSG00000027646


  1. Robo4: a guidance receptor that regulates angiogenesis. Weitzman M, Bayley EB, Naik UP. Cell Adh Migr. 2008;2(4):220–2. PubMed Europe PMC Scholia