Pericytes are specialised cells that wrap around the endothelial cells of the vasculature to regulate vascular integrity, permeability and blood flow. Despite this crucial role, the molecular mechanisms that control pericyte development are not well understood. In this issue, two papers identify a requirement for Notch in pericyte development in the brain and kidney vasculature.

On p. 307, Bruce Appel and colleagues investigate the role of Notch in regulating pericyte number in the developing zebrafish brain vasculature. The authors interrogate a panel of Notch genes and identify notch3 as expressed in the developing vasculature, specifically in cells positive for pdgfrb, a known pericyte marker. Loss-of-function of Notch3 leads to disruption of the blood-brain barrier and cerebral haemorrhaging, which is likely to be due to the reduction in pericyte number. Importantly, the authors show that Notch3 is required for pericyte development and specifically for promoting proliferation and expansion of the cells. Using pdgfrb expression as a readout, the authors observe that overexpression of the Notch3 intracellular domain is associated with increased numbers of pericytes, whereas interference with Notch3 activity causes a reduction. Based on varying levels of pdgfrb expression observed throughout the study, the authors hypothesize that Notch3 may positively regulate pdgfrb in order to regulate pericyte proliferation.

The role of Notch signalling in pericyte development is also investigated by Raphael Kopan and colleagues (p. 346), who report a critical requirement for Notch during the development of the pericytes of the mammalian kidney, known as mesangial cells. These cells, along with the smooth muscle and interstitial cells of the kidney, derive from Foxd1+ stromal precursors; however, Notch signalling appears to be only required for the emergence of the mesangial cells. Inactivation of Notch specifically in the stromal precursors results in the formation of glomeruli that lack mesangial cells, leading to glomerular aneurism and kidney failure at birth. The authors go on to show that, in this case of pericyte development in the kidney, Notch1 and Notch2 appear to act redundantly.