Notch1 and Jagged1 expression by the developing pulmonary vasculature.
The molecular mechanisms of pulmonary vascular development are poorly understood. Cell-specific developmental pathways are influenced by cell-cell signaling. Notch signaling molecules are highly conserved receptors active in many cell-fate determination systems. Recent observations of Notch molecules and a Notch ligand, Jagged1, suggest their importance in vascular morphogenesis, and particularly pulmonary vascular development. We performed a systematic evaluation of Notch1/Jagged1 gene and protein expression in the developing mouse lung from embryonic day 11 until adulthood by using quantitative PCR, immunofluorescence, and electron microscopic analysis. mRNA transcripts for Notch1-4 and Jagged1 increased progressively from early to later lung development, accompanied by a simultaneous rise in endothelial cell-specific gene expression, a pattern not seen in other organs. Notch1 mRNA was identified on both epithelial and mesenchymal structures of the embryonic lung. Immunofluorescence staining revealed the progressive acquisition of Notch1 and Jagged1 proteins by the emerging endothelium. Notch1 and Jagged1 were seen initially on well-formed, larger vessels within the embryonic lung bud and progressively on finer vascular networks. Each was also expressed on surrounding nonvascular structures. The localization of Notch1 and Jagged1 on endothelial cell surface membranes within the alveolar microvasculature was confirmed by immuno-electron microscopy. These temporal and spatial patterns in Notch1/Jagged1 gene and protein expression suggest multiple potential paths of cell-cell signaling during lung development and vascular morphogenesis.
Taichman
Darren B
DB
Pulmonary, Allergy and Critical Care Division, University of Pennsylvania Medical Center, Children's Hospital of Philadelphia and the University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA. dtaichma@mail.med.upenn.edu
Loomes
Kathleen M
KM
Schachtner
Susan K
SK
Guttentag
Susan
S
Vu
Colynda
C
Williams
Patrick
P
Oakey
Rebecca J
RJ
Baldwin
H Scott
HS
D000818:Animals; D001921:Brain / Q000196:embryology; D002135:Calcium-Binding Proteins; D002462:Cell Membrane / Q000378:metabolism; D004730:Endothelium, Vascular / Q000196:embryology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D007668:Kidney / Q000196:embryology; D008168:Lung / Q000098:blood supply* / Q000196:embryology*; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000378:metabolism; D051379:Mice; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D014176:Protein Biosynthesis; D011506:Proteins; D012333:RNA, Messenger / Q000378:metabolism; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D051880:Receptors, Notch; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction; D013997:Time Factors; D014157:Transcription Factors
D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606274:Jag1 protein, mouse; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; C497762:Notch1 protein, mouse; D011506:Proteins; D012333:RNA, Messenger; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins; D014157:Transcription Factors