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PMID: 18544451 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Misexpression of ELF5 disrupts lung branching and inhibits epithelial differentiation.

Developmental biology ·Vol. 320 ·No. 1 ·2008-08-01 ·Pages 149-60

Metzger DE, Stahlman MT, Shannon JM

Abstract

ELF5, an Ets family transcription factor found exclusively in epithelial cells, is expressed in the distal lung epithelium during embryogenesis, then becomes restricted to proximal airways at the end of gestation and postnatally. To test the hypothesis that ELF5 represses distal epithelial differentiation, we generated a transgenic mouse model in which a doxycycline inducible HA-tagged mouse Elf5 transgene was placed under the control of the lung epithelium-specific human SFTPC promoter. We found that expressing high levels of ELF5 during early lung development disrupted branching morphogenesis and produced a dilated epithelium. The effects of ELF5 on morphogenesis were stage-dependent, since inducing the transgene on E16.5 had no effect on branching. ELF5 reduced expression of the distal lung epithelial differentiation markers Erm, Napsa and Sftpc, and type II cell ultrastructural differentiation was immature. ELF5 overexpression did not induce the proximal airway epithelial markers Ccsp and Foxj1, but did induce expression of p63, a marker of basal cells in the trachea and esophagus. High ELF5 levels also induced the expression of genes found in other endodermal epithelia but not normally associated with the lung. These results suggest that precise levels of ELF5 regulate the specification and differentiation of epithelial cells in the lung.

MeSH Terms
Animals Cell Differentiation Cell Proliferation DNA-Binding Proteins/genetics,metabolism Epithelial Cells/cytology Epithelium/embryology Gene Expression Regulation, Developmental Humans Lung/cytology,embryology Mice Morphogenesis Oligonucleotide Array Sequence Analysis Promoter Regions, Genetic/genetics Proto-Oncogene Proteins c-ets/metabolism Pulmonary Surfactant-Associated Protein C/genetics,metabolism Transcription Factors/genetics,metabolism
Chemicals
DNA-Binding Proteins Elf5 protein, mouse Proto-Oncogene Proteins c-ets Pulmonary Surfactant-Associated Protein C SFTPC protein, human Transcription Factors
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Metzger David E
Division of Pulmonary Biology, Cincinnati Children's Hosptial Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, USA.
Stahlman Mildred T
Shannon John M
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Article Info
Journal
Developmental biology
Abbr.
Dev Biol
ISSN
1095-564X
DOI
10.1016/j.ydbio.2008.04.038
Published
2008-08-01
Epub
2008-00-10
Pages
149-60
Language
English
Region
United States
NLM ID
0372762
PMCID
PMC2586150
Subset
IM
Grants
NHLBI NIH HHS · R01 HL084376 · United States
NHLBI NIH HHS · R01 HL084376-02 · United States
NHLBI NIH HHS · T32 HL007752 · United States
NHLBI NIH HHS · HL07752 · United States
External Links
PubMed source DOI: 10.1016/j.ydbio.2008.04.038 PMC Full Text View journal details
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