Mammalian lung development: Interactions in primordium formation and bronchial morphogenesis

Abstract

The manner in which mouse lung primordia form has been analyzed by observation of trypsin-isolated gut endoderm from nine-day embryos. The tissue interactions involved in initial formation of lung primordia and those involved in subsequent morphogenesis of the primordia have been investigated by various organ culture procedures. Mouse lungs form in a manner different from that generally described for amniote embryos. Thus, two lung buds appear first and form the primary bronchi, whereas the trachea appears secondarily.The initial lung buds form at the 25-27 somite stage. Whole-guts from embryos as young as the two-somite stage form lung buds in culture. Such buds do not undergo branching morphogenesis if the guts are taken from embryos younger than the 25-somite stage, but undergo characteristic dichotomous branching if combined with older bronchial mesoderm. If 20-25 somite-stage endoderm is isolated and cultured in direct combination with gut, older salivary or older bronchial mesoderms, lung buds form. However, such buds only branch in combinations containing bronchial mesoderm. Our results reveal two levels of mesodermal control of lung development. Interactions between nonspecific mesoderm and gut endoderm result in lung bud formation, while those between specific bronchial mesoderm and bud endoderm are required for branching morphogenesis.

Targeted expression of a dominant negative FGF receptor blocks branching morphogenesis and epithelial differentiation of the mouse lung.

“…In embryonic lung explants, bronchial mesoderm is required for branching of the lung buds, demonstrating the importance of epithelial/mesenchymal interaction in lung development (Alescio and Cassini, 1962;Spooner and Wessels, 1970;Alescio and Dani, 1971). Our present findings suggest that FGFs are likely mediators of this crucial interaction.…”

Developmental Pathways and Specification of Intrapulmonary Stem Cells

“…Growth and differentiation of the lung endoderm is strictly dependent on signaling from the mesenchyme. Classical recombination experiments mixing lung endoderm with distal versus proximal lung mesenchyme showed that the mesenchyme provides instructional cues for endodermal morphogenesis and cell lineage determination (14). It is important to note that the mesenchyme is also a source of cells contributing to a number of functional compartments in the lung including the vasculature and the airway smooth muscle.…”

The Mammalian Respiratory System and Critical Windows of Exposure for Children's Health

“…This dual origin of lung tissues is critical in development. Removal of mesenchyme from the tip of a lung bud during early phases of development with transplantation to the side of a higher ordered segment abolishes further branching at the site of removal while stimulating growth of a new branch at the site of transplantation (14). Lung (4).…”