A hypothetical model showing bone marrow megakaryocytes transitioning (left to right) from the endosteal to vascular niche generating podosome structures in response to ECM and vascular sinusoidal basement membrane. When megakaryocytes breach the basement membrane, they extend proplatelet arms through the sinusoidal endothelium into the bloodstream. In response to ECM cues, megakaryocytes generate classical podosome structures containing actin cores induced by Arp2/3 and WASp (bottom left). These podosome structures degrade ECM and basement membrane via secreted and/or transmembrane MMPs. Putative crosstalk between these protease releasing structures and proplatelet arms extending into vessels (bottom right) remains to be determined. Professional illustration by Marie Dauenheimer.