Integrin Beta 1 Suppresses Multilayering of a Simple Epithelium

Jichao Chen,Mark A Krasnow,Saverio Bellusci

doi:10.1371/journal.pone.0052886

Abstract

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.

Highlights

Epithelia cover the external and internal surfaces of all multicellular organisms, and they separate compartments by forming physical and physiological barriers
We found that the nuclei of some (,10%) mitotic cells in the integrin beta 1 (Itgb1) mutant lung epithelium were positioned more than one nuclear diameter away from the lumenal surface of the epithelium, whereas mitotic cell nuclei in the control epithelium were always located within one nuclear diameter, implying a defect in interkinetic nuclear migration [25] (Figure 2A and B; p = 0.0001)
We have shown that conditional deletion of integrin Itgb1 throughout the developing airway epithelium abolishes airway branching and converts this monolayer epithelium into a multilayer structure with more than 10 extra layers

Summary

Introduction

Epithelia cover the external and internal surfaces of all multicellular organisms, and they separate compartments by forming physical and physiological barriers. Epidermal progenitor cells switch from symmetric cell division, where the mitotic spindle orients parallel to the basement membrane and gives rise to functionally equivalent daughter cells, to predominantly asymmetric cell division, where the mitotic spindle orients perpendicular to the basement membrane and generates a self-renewing basal cell and a differentiating supra-basal cell; this transition depends on protein complexes controlling cell polarity and spindle positioning [2,3,4] In addition to these cellular changes, epidermal progenitor cells switch their keratin profile by downregulating keratin genes specific for simple epithelia (Krt and Krt18), and activating ones specific for stratified epithelia (Krt and Krt14) [5]. Little is known about the simple-versus-stratified decision in other developmental contexts

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Results

Conclusion