The evolution of connective tissue cells in the developing fetal rat lung is studied under the electron microscope from the 15th until the 21st day of gestation and is compared to the evolution of epithelial cells. Three successive types of stem cells ("mesocytoblasts") are present during the first stages of lung development studied (15 to 18 days of gestation). These stem cells appear to be able to differentiate into fibroblasts or into smooth muscle cells, according to their localization along the broncho-alveolar tubule. Myoblasts are situated near the bronchial epithelium, whereas fibroblasts occur under the alveolar epithelium. Epithelo-mesenchymal interactions are assumed to play a role in this differentiation process. Synthesis of both, collagen and elastic fibers and of cytoplasmic filaments by fibroblasts as well as by myoblasts reveal the multiple potentialities of the mesenchymal stem cell and suggest a common origin. The early fibroblast in characterized by long cytoplasmic processes which contain numerous cytofilaments, and by the presence of collagen fibers in the vicinity of the cell. Later on, (20 days of gestation) the mature fibroblast of the lung mesenchyme shows areas of RER, glycogen and lipidic vacuoles in its cytoplasm. Cytofilaments are numerous within very long cytoplasmic processes and elastic and collagen fibers are very frequent beside the cytoplasmic membrane. The earliest fibroblast differentiation occurs under the epithelium of primitive respiratory bronchioles, which indicate the limit between the bronchial and the alveolar territories. Later on, differentiating fibroblasts are found throughout the whole alveolar walls. Connective tissue cells other than mesenchymal stem cells, fibroblasts or myoblasts are observed during lung development. Vacuolar cells, similar to Hofbauer cells, transiently appear on the 16th day of gestation. On the 20th and the 21st day macrophage-like cells are present in the septal space of the alveolar wall. The absence of intermediate stages of differentiation and parallel evolution of blood cells suggest that those connective tissue cells are differentiated elsewhere and have then migrated from blood into lung mesenchyme. No cell death has been observed in the developing lung.
