The vasculature of the central nervous system (CNS) is highly specialised, characterised by the formation of the blood-brain barrier that prevents leakage of vascular contents into the brain. Various molecules and pathways have been implicated in regulating angiogenesis in the CNS, including the αVβ8 integrin and members of the TGFβ pathway. It is thought that αVβ8 integrin expressed in the neuroepithelium regulates TGFβ signalling in the endothelium. On p. , Thomas Arnold, Louis Reichardt and colleagues set out to investigate this relationship and the effects of disrupting this signalling cascade on the CNS vasculature. The authors find that disruption of either the integrin or TGFβ pathway components leads to excess angiogenic sprouting, vascular dysplasia and cerebral haemorrhage. Importantly, however, these mutant mice display no signs of compromised blood-brain barrier formation and the vessels, although abnormal, are not leaky. Together, this work defines an important function for αVβ8 integrin-TGFβ signalling in limiting vascular sprouting in the CNS, and demonstrates that cerebral haemorrhage can result from abnormal angiogenesis rather than from blood-brain barrier breakdown.
