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PMID:18374910

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Citation

Gontan, C, de Munck, A, Vermeij, M, Grosveld, F, Tibboel, D and Rottier, R (2008) Sox2 is important for two crucial processes in lung development: branching morphogenesis and epithelial cell differentiation. Dev. Biol. 317:296-309

Abstract

The primary lung bud originates from the foregut and develops into the bronchial tree by repetitive branching and outgrowing of the airway. The Sry related HMG box protein Sox2 is expressed in a cyclic manner during initiation and branching morphogenesis of the lung. It is highly expressed in non-branching regions and absent from branching regions, suggesting that downregulation of Sox2 is mandatory for airway epithelium to respond to branch inducing signals. Therefore, we developed transgenic mice that express a doxycycline inducible Sox2 in the airway epithelium. Continuous expression of Sox2 hampers the branching process resulting in a severe reduction of the number of airways. In addition, the bronchioli transiently go over into enlarged, alveolar-like airspaces, a pathology described as bronchiolization of alveoli. Furthermore, a substantial increase was observed of cGRP positive neuroendocrine cells and Delta Np63 isoform expressing (pre-) basal cells, which are both committed precursor-like cells. Thus, Sox2 prevents airways from branching and prematurely drives cells into committed progenitors, apparently rendering these committed progenitors unresponsive to branch inducing signals. However, Sox2 overexpression does not lead to a complete abrogation of the epithelial differentiation program.

Links

PubMed Online version:10.1016/j.ydbio.2008.02.035

Keywords

Animals; Cell Differentiation; DNA-Binding Proteins/genetics; DNA-Binding Proteins/metabolism; Embryo, Mammalian/metabolism; Epithelial Cells/cytology; HMGB Proteins/genetics; HMGB Proteins/metabolism; Lung/cytology; Lung/embryology; Mice; Mice, Transgenic; Morphogenesis; SOXB1 Transcription Factors; Transcription Factors/genetics; Transcription Factors/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:SOX2

acts_upstream_of_or_within

GO:0045165: cell fate commitment

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SOX2

acts_upstream_of_or_within

GO:0030858: positive regulation of epithelial cell differentiation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SOX2

acts_upstream_of_or_within

GO:0048286: lung alveolus development

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SOX2

acts_upstream_of_or_within

GO:0060441: epithelial tube branching involved in lung morphogenesis

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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