Figure 5: Interstitial ECM dynamics (signaling) and tubulogenesis.

(A) Mouse submandibular gland form is sculpted by fibronectin-dependent regulation of epithelial morphology. Insets: Cleft formation is orchestrated by the local enrichment of fibronectin, which leads to the downregulation of E-cadherin. Low E-cadherin levels allow the labile epithelial cells to accommodate clefting.

(B) Mouse lung alveolarization occurs following the growth factor-dependent early branching morphogenesis mediated by the interstitial ECM. Inset: Sacculation, which marks the development of alveolar sacs in association with the pulmonary vasculature, is shaped largely by an elastin-rich interstitial matrix crest that forms an organized network at the alveolar ridges.

(C) Branching morphogenesis of the ureteric bud leads to mouse kidney assembly, and is driven by glial cell line-derived neurotrophic factor (GDNF) signaling; The interstitial extracellular matrix hosts remodeling factors and facilitates cell-cell and cell-matrix morphogenetic signaling.

(D) Mammary gland duct branching morphogenesis is mediated by the collagen-rich interstitial ECM—the major component of the fat pad mesenchyme.