Role for ephrinB2 in postnatal lung alveolar development and elastic matrix integrity

Wilkinson, George A; Schittny, Johannes C; Reinhardt, Dieter P; Klein, Rüdiger (2008). Role for ephrinB2 in postnatal lung alveolar development and elastic matrix integrity. Developmental dynamics, 237(8), pp. 2220-34. New York, N.Y.: John Wiley & Sons 10.1002/dvdy.21643

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Alveoli are formed in the lung by the insertion of secondary tissue folds, termed septa, which are subsequently remodeled to form the mature alveolar wall. Secondary septation requires interplay between three cell types: endothelial cells forming capillaries, contractile interstitial myofibroblasts, and epithelial cells. Here, we report that postnatal lung alveolization critically requires ephrinB2, a ligand for Eph receptor tyrosine kinases expressed by the microvasculature. Mice homozygous for the hypomorphic knockin allele ephrinB2DeltaV/DeltaV, encoding mutant ephrinB2 with a disrupted C-terminal PDZ interaction motif, show severe postnatal lung defects including an almost complete absence of lung alveoli and abnormal and disorganized elastic matrix. Lung alveolar formation is not sensitive to loss of ephrinB2 cytoplasmic tyrosine phosphorylation sites. Postnatal day 1 mutant lungs show extracellular matrix alterations without differences in proportions of major distal cell populations. We conclude that lung alveolar formation relies on endothelial ephrinB2 function.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy > Functional Anatomy

UniBE Contributor:

Schittny, Johannes

ISSN:

1058-8388

ISBN:

18651661

Publisher:

John Wiley & Sons

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:03

Last Modified:

04 May 2014 23:19

Publisher DOI:

10.1002/dvdy.21643

PubMed ID:

18651661

Web of Science ID:

000258482300029

URI:

https://boris.unibe.ch/id/eprint/27532 (FactScience: 108748)

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