The Response of Primary Mesenchyme Cells to VEGF

Overview: Spiculogenesis in the sea urchin embryo, i.e. the formation of a complex endoskeleton secreted by primary mesenchyme cells (PMC), is the result of a morphogenetic program that begins with maternal inputs to regulatory genes in the early zygote and leads to the specification of the large micromere-PMC lineage. The current model of the skeletogenic gene regulatory network (GRN) involves about 80 genes. Recent efforts have identified downstream targets of this GRN that are more directly involved in morphogenesis and terminal differentiation. However, the local influence of ectoderm-derived factors is not well understood. We recently discovered that recombinant sea urchin vascular endothelial growth factor (rVEGF) has a dramatic concentration-dependent effect on the shape of spicules grown in PMC in vitro culture. Triradiates, i.e. branching spicules that closely resemble those initially deposited in the embryo, require a threshold concentration of rVEGF. Below this concentration, markedly different spicule shapes are formed. Remarkably, the change in shape is accompanied by a change in the crystallographic growth direction of the spicule. VEGF is, thus, an important extrinsic regulator of morphogenetic events in PMC.