Vascular smooth muscle is derived, in part, from the neural crest in a differentiation programme regulated by the Jagged1-Notch signalling pathway. However, there is also evidence that Hippo signalling regulates vascular smooth muscle development. Several studies have detailed mechanisms by which the Hippo and Notch pathways interact and, on p. , Jonathan Epstein and colleagues identify a new level of cross-talk between these two pathways – via direct interaction between Yap (a Hippo pathway-regulated transcription factor) and the Notch intracellular domain (NICD). They first show in mice that deletion of Yap and the functionally related protein Taz in the neural crest leads to loss of crest-derived vascular smooth muscle; this phenotype is reminiscent of that caused by deletion of Rbp-J – the transcription factor downstream of Notch. They then provide evidence in cell culture models that Yap and NICD physically interact and co-occupy the enhancers of a subset of known Notch target genes, and that the Yap/NICD/Rbp-J complex is important for induction of vascular smooth muscle differentiation. Thus, as well as shedding light on how the vascular smooth muscle forms, this work provides insights into the mechanisms of signalling pathway cross-talk and its importance during development.
