Haemorrhagic stroke, which occurs when a blood vessel bursts within the brain, is frequently associated with intracranial vascular malformations. On , Whitehead et al. turn the developmental spotlight onto one such malformation - cerebral cavernous malformation (CCM). Human CCM is characterised by enlarged,thin-walled vascular structures in the central nervous system and has been linked to loss-of-function mutations in the CCM1 locus. Whitehead and colleagues report that the earliest defects in Ccm1-/-mouse embryos (seen at E8.5) are vascular; in particular, the precursor vessels of the brain become dilated. These defects are reminiscent of human CCMs and are associated with disruption of arterial specification. Consistent with this, expression of Notch4, a marker of arterial specification,is downregulated in the arterioles of people with CCM1 mutations. Thus, CCM may result from defects in arterial specification and the authors suggest that the same may be true for other vascular malformations.
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