Adhesive properties of cells undergoing morphogenetic rearrangements can be regulated either at the cellular level or by altering the environment in which rearrangements occur. Here, we describe the identification of a mutation ( my F11 ) in the mouse extracellular matrix component Frem2, and provide evidence that suggests Frem2 expression creates an environment conducive to morphogenetic events. Loss of Frem2 function results in defects in developmental events associated with morphogenetic rearrangements of the vasculature and of tissues arising from all germ layers. The Frem2 transcript is restricted both spatially and temporally and appears in advance of cell rearrangement events. Thus, expression of Frem2 may dynamically alter the extracellular matrix to provide a substrate for cell migration and rearrangements during embryogenesis.