Figure 4. Disruption of the actin cytoskeleton and reduced cell-cell and cell-matrix contacts in Srf mutant mice.

(A) Phalloidin-FITC staining of skin sections of control and Srf mutant mice at P14 shows markedly reduced levels of polymerized actin (F-actin) in lesions of Srf mutant skin (upper panels). Immunofluorescence staining for E-cadherin shows membrane localization in skin of control and Srf mutant mice (lower panels). Dotted lines indicate the basement membrane. Scale bar: 20 μm. (B–E) Ultrastructural analysis of control and Srf mutant epidermis at P14. (B) Keratinocytes in the basal cell layer of lesional Srf mutant epidermis are strongly enlarged and lack most cell-cell contacts compared with control skin, in which basal keratinocytes are small and densely packed. Arrows indicate the basement membrane. (C) Stratum corneum (sc) of lesional Srf mutant epidermis is thicker and less compact than stratum corneum of control epidermis. (D) Epidermal lesions of Srf mutant skin show areas with defective hemidesmosomes (arrows). Note that collagen bundles below the basement membrane are absent in Srf mutant skin. (E) Desmosomes (arrows) are markedly reduced in Srf mutant skin, and cell-cell contacts are largely absent. (F and G) Morphometric analysis confirmed a distinct reduction of the number of desmosomes (F), while no change of the mean length of single desmosomes could be found (G). Error bars indicate SD. Scale bars: 5 μm (B and C); 1 μm (D and E). ***P ≤ 0.001.