Susan K Schachtner | PubMed Health

PubMed2003

A unique pattern of Tie1 expression in the developing murine lung.

The molecular mechanisms responsible for organ-specific differences in vascular development are not well established. Animals lacking the receptor tyrosine kinase Tie1 die of hemorrhage and pulmonary edema. Furthermore, cells lacking Tie1 are excluded from blood vessels of the mature lung. These findings suggest the importance of Tie1 in the pulmonary vasculature. We quantified the organ-specific expression of Tie1 during embryonic and postnatal murine development using both quantitative real-time polymerase chain reaction (PCR) and chemiluminescence employing a tie1.lacZ reporter. In the lung, Tie1 expression increases markedly immediately prior to birth and rises further in the newborn animal, a pattern not found in other organs. Furthermore, expression of Tie1 in the lung is also unique by its persistent increase in the adult animal. This unique pattern of Tie1 gene expression in the embryonic and mature lung supports a distinct role for Tie1 in the development and function of the pulmonary vasculature.

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PubMed2002

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.

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