Fig. 2. Lack of extracellular matrix, weak cell adhesion and poorly developed endoplasmic reticulum in fibroblasts of Foxf mutant gut. TEM images of E18.5 wild-type (A,C,E) and Foxf1^-/+; Foxf2^-/+ (B,D,F) distal colon. (A) Normal stratified colon with (from top) epithelium, mesenchyme, the two muscle layers and mesothelium (compare Fig. 1J). (B) Foxf1^-/+; Foxf2^-/+ colon with flat epithelium (top right) and poorly differentiated, dissociating SMCs (compare with Fig. 1K). (C) A basement membrane (white arrowheads) delimits the epithelium (top) from the mesenchymal layer and bundles of fibrillar collagens (black arrowheads) are embedded in the basal laminae surrounding individual fibroblasts and smooth muscle cells. Endoplasmic reticulum in fibroblasts is well developed and filled with electron-dense proteins for secretion (arrow). (D) Hardly any ECM or collagen fibers can be seen in the mutant colon. The basement membrane is indistinct and instead gaps of extracellular space (white arrowheads) separate epithelium (top) from mesenchyme. Gaps are also frequent between mesodermal cells (black arrowhead). (E) Wild-type fibroblasts have well-developed endoplasmic reticulum (white arrowheads), often filled with proteins (arrow). (F) Foxf mutant colon mesodermal cells have a poorly differentiated SMC phenotype with little endoplasmic reticulum (white arrowhead).