Integrin Beta 1 Suppresses Multilayering of a Simple Epithelium
Figure 4
The multilayer epithelium in the Itgb1CKO/−; ShhCre/+ mutant lung expresses markers of simple epithelium.
(A) Stereoscope (left; scale bar, 100 um) and confocal (right; scale bar, 20 um) images of E13 whole-mount lungs immunostained for E-Cadherin (ECAD) and P63. The boxed regions in the left panels are imaged by confocal microscopy and shown in the right panels. P63 is expressed in the esophagus (top), but not in the branching regions of the lungs (bottom), of both control and Itgb1CKO/−; ShhCre/+ mutant embryos. (B) Whole-mount in situ hybridization shows that the epithelia of both control and Itgb1CKO/−; ShhCre/+ mutant lungs express a marker of simple epithelium (Krt8), but not a marker of stratified epithelium (Krt5) at E13. Scale bar, 100um. (C) A three-part model of epithelial stratification comparing epidermis and lung. Layer formation: regulation of mitotic spindle orientation (blue carets) drives formation of a multilayer epithelium; layer diversification: cell autonomous and/or non-autonomous signals lead to molecular and functional specialization of cells of different layers (green squares, cells with low Notch (N) pathway activity (epidermis) or high FGF pathway activity (lung); red dashed circles, cells undergoing cell death and cornification (epidermis) or cell death alone (lung)); layer maturation: activation of genes such as keratin genes specific for stratified epithelia and suppression of ones for simple epithelia leading to differentiation of the layers (shaded cells). Although the maturation step is shown last, the keratin profile switch in epidermis initiates in the monolayer and continues throughout stratification. In the absence of Itgb1, the normally simple lung epithelium may be in a random, disorganized state. However, the Itgb1 mutant epithelium shares two of the three features of epidermal stratification, suggesting that it undergoes partial stratification. epi, epithelium; bm, basement membrane; mes, mesenchyme.