Figure 2.

ECM dynamics determine epithelial branch patterning in vertebrate organs. The ECM is dynamic and plays essential roles in various steps during vertebrate epithelial branching morphogenesis. Deposition of newly synthesized ECM (green solid line) including fibronectin and laminin is required for splitting the epithelial bud and primary branching (1). In contrast, partial degradation of the ECM (gray dotted line) by MMP is necessary for epithelial cells to sprout from the side of the duct and undergo side branching (2). MMP activities are also required at the invasion front to maintain a constant ECM remodeling process that is essential for collective epithelial migration (3). MMP activities also generate functional ECM fragments to promote cell proliferation in the tip epithelial cells and thus are essential for supplying the necessary building blocks to sustain the rapid progress of epithelial branching. Interestingly, newly synthesized ECM is also deposited around the “neck” of the branching tip (4). ECM deposition at this place may be important for the ductal remodeling process that has been observed in kidney epithelial branching. (Figure was revised from the original version created by Mark Sternlicht [Sternlicht et al. 2006] and reprinted, with permission, from Elsevier © 2006.)