Format

Send to

Choose Destination
Am J Physiol Lung Cell Mol Physiol. 2010 Jan;298(1):L45-56. doi: 10.1152/ajplung.90550.2008. Epub 2009 Nov 6.

Lunatic Fringe-mediated Notch signaling is required for lung alveogenesis.

Author information

1
Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, 101 College St., East Tower, Rm. 14-309, Toronto, Ontario, Canada M5G 1L7.

Abstract

Distal lung development occurs through coordinated induction of myofibroblasts, epithelial cells, and capillaries. Lunatic Fringe (Lfng) is a beta(1-3) N-acetylglucosamine transferase that modifies Notch receptors to facilitate their activation by Delta-like (Dll1/4) ligands. Lfng is expressed in the distal lung during saccular development, and deletion of this gene impairs myofibroblast differentiation and alveogenesis in this context. A similar defect was observed in Notch2(beta-geo/+)Notch3(beta-geo/beta-geo) compound mutant mice but not in Notch2(beta-geo/+) or Notch3(beta-geo/beta-geo) single mutants. Finally, to directly test for the role of Notch signaling in myofibroblast differentiation in vivo, we used ROSA26-rtTA(/+);tetO-CRE(/+);RBPJkappa(flox/flox) inducible mutant mice to show that disruption of canonical Notch signaling during late embryonic development prevents induction of smooth muscle actin in mesenchymal cells of the distal lung. In sum, these results demonstrate that Lfng functions to enhance Notch signaling in myofibroblast precursor cells and thereby to coordinate differentiation and mobilization of myofibroblasts required for alveolar septation.

PMID:
19897741
PMCID:
PMC2806195
DOI:
10.1152/ajplung.90550.2008
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Atypon Icon for PubMed Central
Loading ...
Support Center