Developmental heterogeneity of mesenchymal glycosaminoglycans (GAG) distribution in chick embryo lung anlagen

Abstract

The presence and distribution of mesenchymal components in the extracellular matrix during lung development in the chick embryo (from 5 1/2/6 to 18 incubation days) has been examined histochemically. Attention is focused mainly on glycosaminoglycans (GAG). Morphological reconstructions show three main stages: first (5 1/2/6-8 days), formation of 2nd-order branching; second (9-12 days), proliferation of parabronchi and third (from 13th day on), formation of air capillaries. In the first phase, hyaluronic acid (HA) prevails around the mesobronchus, but chondroitin sulfate (CS) dominates the 2nd-order branches. Basement membranes of 2nd-order branches are strongly positive for sulphated GAG. In the second phase, CSA increases in the ground substance of mesenchyme. This increase is irregular, being smaller in older areas (mesobronchus, branches of 2nd order) and larger in the more recent parabronchi, which extend into the lateral and dorsal areas of the rudiment. An increase in both sulfated GAG and glycoprotein (GP) occurs in basement membranes. In the third phase, GAGs are uniformly distributed in the mesenchymal septa and around the interlobular vascular network. This concentration decreases while the GP concentration increases. Basement membranes around every branch of the 1st, 2nd, and 3rd orders possess large quantities of GP. Mesenchymal GAG occurs in every stage of lung development, temporally correlating with the morphogenesis and differentiation of epithelium. Our results provide necessary information, which has not been available so far. Experimental studies specifically designed to clarify the developmental significance of such a heterogeneous distribution may be interpreted in the light of this information.

Inhibitory morphogens and monopodial branching of the embryonic chicken lung

“…Secondary bronchi (both ventrobronchi and dorsobronchi) continued to elongate and branch from and around the main bronchi until HH33, when additional branching from the primary bronchus could not be discerned and other structures such as the air sacs and recurrent bronchi became evident. These observations of the airways visualized using E-cadherin staining are consistent with descriptions gleaned from previously published work using cedar oil or alcian blue histochemistry (Locy and Larsell, 1916a; Locy and Larsell, 1916b; Becchetti et al, 1988). …”

“…All cultured explants initially contained one or two secondary bronchi on each primary bronchus. This tight control over the initial morphology of the explants ensured that morphogenesis was limited to monopodial branching from the primary bronchi, and did not include the additional branching or anastomosis of secondary bronchi characteristic of later developmental stages (Figure 1) (Locy and Larsell, 1916a; Locy and Larsell, 1916b; Becchetti et al, 1988). Whereas development of the initial branching pattern of the lung is completed in less than three days in vivo (E4+ to E7), lungs cultured ex vivo developed more slowly.…”

Transforming growth factor ?2, but not ?1 and ?3, is critical for early rat lung branching

“…Several studies have reported that GAG synthesis in vivo alters with development, suggesting that GAGs play a role in organogenesis. Hyaluronan is prominent early in lung morphogenesis and is mostly localized in the growing areas of the lung, whereas chondroitin sulfate proteoglycans are deposited in areas of second order branching (Becchetti et al, 1988). Inhibitors of GAG synthesis such as 6-diazo-5-oxo-L-norleucine and azaserine inhibit branching morphogenesis of cultured embryonic lung rudiments (Spooner et al, 1986).…”

Epithelial-mesenchymal interactions: a fundamental Developmental Biology mechanism

“…The composition of the extracellular glycosaminoglycans (GAGs) varies during different phases of lung development and influence branching and differentiation of lung epithelium (Becchetti et al, 1988, Shannon, 1994.…”