Proposed morphogenic mechanism mediated by MMP2. Our working hypothesis is that LEC behavior is driven by physical constraints imposed by the matrix barrier. Lymphatic vessel elongation and/or branching are dictated by the composition of ECM components, the quantity and cross-linking of the components and where they are situated around the developing vessels. The structural and molecular determinants promote: (1) a stationary phenotype in dense matrix; (2) a bifurcation in case of local matrix deposition as delineated by * (see also Figure 4I-J); and (3) a mesenchymal-like migratory phenotype in case of controlled matrix degradation.