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Fig. 7. Working model for roles of cell migration and fibronectin translocation in branching morphogenesis. Cells engage in active migration, providing a highly plastic tissue that is susceptible to local matrix signals. Three representative motile cells have been colored in yellow, blue and cyan. As cleft formation begins, FN is located at the cleft initiation site. Cleft formation proceeds towards the center of the gland with continued synthesis and assembly of FN fibrils by neighboring epithelial cells and dynamic inward progression of an aggregate or wedge of FN between mobile epithelial cells. FN washout experiments show that older FN (green) is translocated deep into the gland at the base of deepening clefts, whereas new FN (red) assembly occurs behind it. We propose that the dynamic inward translocation of FN as a wedge, followed by later assembly behind it, provides the missing mechanism for precise local deposition of FN synthesized by a broad zone of cells surrounding developing clefts. The local wedge of FN would mediate the previously described conversion of E-cadherin cell-cell adhesions to integrin-mediated cell-matrix adhesions, thereby promoting the separation of actively jostling cells to form the cleft during branching morphogenesis.
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