Integrin Beta 1 Suppresses Multilayering of a Simple Epithelium

Department of Biochemistry and HHMI, Stanford University School of Medicine, Stanford, California, United States of America.
PLoS ONE (Impact Factor: 3.23). 12/2012; 7(12):e52886. DOI: 10.1371/journal.pone.0052886
Source: PubMed


Epithelia are classified as either simple, a single cell layer thick, or stratified (multilayered). Stratified epithelia arise from simple epithelia during development, and transcription factor p63 functions as a key positive regulator of epidermal stratification. Here we show that deletion of integrin beta 1 (Itgb1) in the developing mouse airway epithelium abrogates airway branching and converts this monolayer epithelium into a multilayer epithelium with more than 10 extra layers. Mutant lung epithelial cells change mitotic spindle orientation to seed outer layers, and cells in different layers become molecularly and functionally distinct, hallmarks of normal stratification. However, mutant lung epithelial cells do not activate p63 and do not switch to the stratified keratin profile of epidermal cells. These data, together with previous data implicating Itgb1 in regulation of epidermal stratification, suggest that the simple-versus-stratified developmental decision may involve not only stratification inducers like p63 but suppressors like Itgb1 that prevent simple epithelia from inappropriately activating key steps in the stratification program.

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    • "A variety of specific defects were identified, including altered branching morphogenesis, impaired alveolarization with epithelial cell differentiation defects and persistent macrophagemediated inflammation, indicating that β1 integrin expression in the lung epithelium plays multiple roles in distinct phases of lung development. Our findings are complementary to a prior study that found that epithelial depletion of β1 integrin beginning at E9.5 causes a serious branching defect and neonatal death (Chen and Krasnow, 2012). Fig. 4. Deleting β1 integrin in lung epithelium causes adhesion and migration defects. "
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