Working model for BMP9 regulation of lymphatic vessel maturation and valve development. In LECs, BMP9 acting via ALK1 inhibits LYVE-1 expression. In parallel, BMP9 also via Alk1, induces the expression of Foxc2, Cx37, ephrinB2, and Nrp-1, which have all been involved in lymphatic valve formation. Flow has been demonstrated to induce Foxc2 expression and to act in concert with Prox1 to regulate early steps of lymphatic valve morphogenesis.⁷  ALK1 expression has been reported to be regulated by flow in zebrafish.²⁶  Therefore, we propose that flow could increase ALK1 expression, which would raise BMP9 signaling to favor the downstream cascade of lymphatic vessel development.