Fig. 5

Graphical summary.

Endothelial cells form filopodia to sense their environments and facilitate chemotaxis-induced migration. In 2D migration assays, BMPR2-deficient cells fail to form filopodia and display an exacerbated collective migration behavior upon lack of BMPR2 expression which impedes with their efficient forward movement. We also found an increased co-localization of actomyosin together with cortical actin at the leading edge of BMPR2 deficient cells. Also, focal adhesion formation is altered. In 3D sprouting assays, BMPR2 deficiency stalls sprouting and abrogates ECs from acquiring the tip cell (TC) position. Wildtype and BMPR2 deficient sprouts perform pulling which is dominated by the tip-cell (TC), while we find no general change in overall pulling forces between BMPR2^wt and BMPR2^+/- sprouts. In spheroid sprouting assays as mosaic, loss of BMPR2 expression by the TC identifies BMPR2 as a gene required for acquiring TC position in competition with stalk cells (SCs). In our proposed molecular model, we identified BMPR2 to regulates CDC42 activity. We propose that CDC42 dependent actin polymerization is facilitated in proximity to filopodia by ref. ¹ inducing non- canonical PI3K signaling and² via yet to be confirmed BMPR2 interacting CDC42 effector protein BORG5, known to promote local actomyosin contractility in ECs.