Published ahead of print on July 29, 2005, doi:10.1165/rcmb.2005-0180OC
Am. J. Respir. Cell Mol. Biol., Volume 33, Number 5, November 2005, 455-462
A more recent version of this article appeared on November 1, 2005
Submitted on May 13, 2005
Revised on July 27, 2005
Conditional Recombination Reveals Distinct Subsets of Epithelial Cells in Trachea, Bronchi, Alveoli
Anne-Karina T Perl1*, Susan E Wert1, David E Loudy1, Zhengyuan Shan1, Paula A Blair1, and Jeffrey A Whitsett1
1 Department of Pediatrics, Division of Pulmonary Biology and Neonatology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
* To whom correspondence should be addressed. E-mail: anne.perl{at}cchmc.org.
To identify relationships amongst tracheal and alveolar epithelial cells during lung development, we utilized conditional systems controlled by the rat CCSP and human SFTPC gene promoters to express Cre-recombinase in the developing mouse lung, thereby permanently labeling cells by expression of alkaline phosphatase or green fluorescent protein. When controlled by the rat CCSP promoter, continuous exposure of the fetus to doxycycline caused wide-spread recombination in conducting airway epithelial cells, including cells of the trachea, bronchi, and bronchioles before birth, and in both conducting and peripheral airways after birth. Neuroepithelial cells, identified by CGRP staining, were never labeled. Recombination and permanent labeling were observed in both ciliated and non-ciliated respiratory epithelial cells, demonstrating their derivation from common progenitor cells during lung morphogenesis. Remarkable dorsal-ventral and cephalo-caudal labeling-patterns, established prior to birth, were identified by recombination controlled by the rat CCSP gene promoter. In the trachea, subsets of epithelial cells labeled by the CCSP promoter were organized horizontally along the dorsal-ventral axis of the trachea, where selective labeling of cells juxtaposed to tracheal and bronchial cartilage was observed. In sharp contrast, recombination controlled by the human SFTPC gene promoter identified related cells that were organized in linear patterns along the cephalo-caudal axis of the conducting airways. Conditional expression of Cre-recombinase in the respiratory epithelium provides a useful model for the study of gene expression and function in the mouse respiratory tract and in the lung.
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