Figure 8. Model of how MNs control blood vessel patterning in the developing SC.

MNs express VEGF to allow blood vessel growth, but at the same time express sFlt1 to titrate the availability of their own produced VEGF in order to pattern the vasculature and prevent premature ingression of vessels into MN columns during a developmental time window. sFlt1 expression is transcriptionally regulated by NRP1. A deregulation of the balance towards higher concentrations of VEGF (VEGF gain-of-function, sFlt1 loss-of-function, or NRP1 loss-of-function (thus reduction of sFlt1)) results in the premature invasion of blood vessels into MN columns, indicating that VEGF levels need to be tightly titrated.