The development of the nervous and the vascular systems exhibit extensive similarities, both on the anatomical and the molecular level. Blood vessels and nerves are structurally similar and often aligned, following parallel routes. The brain is the most vascularized tissue in our body. In the past, we have discovered that the same molecular mechanisms are used to orchestrate the development of the nervous and the vascular system. It is now believed that blood vessels in the brain exert instructive functions that go beyond supplying nutrients and oxygen, for example supplying ligands that directly influence neuronal behavior by activating corresponding receptors and signaling pathways in neuronal cells. We are interested in elucidating the molecular pathways involved in the crosstalk between vessels and nerves and how this crosstalk signaling is integrated among the different cellular players (neurons, endothelial cells, astrocytes) at the neurovascular interface during CNS development and during adult functions such as blood brain barrier maintenance and synaptic plasticity.
1. Segarra et al. (2018) Endothelial Dab1 signaling orchestrates neuro-glia-vessel communication in the central nervous system. Science 361:6404
2. Pfennig et la., (2017) GRIP1 Binds to ApoER2 and EphrinB2 to Induce Activity-Dependent AMPA Receptor Insertion at the Synapse. Cell Reports 21:84-96
3. Geiger et al., (2014) The GRIP1/14-3-3 pathway coordinates cargo trafficking and dendrite development. Dev Cell 28: 381-393.
4. Senturk et al (2011) EphrinBs are essential components of the Reelin pathway to regulate neuronal migration. Nature, 472:356-60; 478:274
5. Sawamiphak et al., (2010) EphrinB2 regulates VEGFR2 function in developmental and tumour angiogenesis Nature 465:487–491
6. Essmann et al., (2008) Serine phosphorylation of ephrinB2 regulates trafficking of synaptic AMPA receptors. Nature Neuroscience 11:1035 – 1043
7. Segura et al (2007) Grb4 and GIT1 transduce ephrinB reverse signals modulating spine morphogenesis and synapse formation. Nature Neuroscience 10: 301-310.