Altered patterns of proteoglycan deposition during maturation of the fetal mouse lung

Previous studies have shown that beta-xyloside inhibits maturation of the fetal mouse lung (Smith et al., Dev. Biol. 138, 42-52, 1990). Insofar as this drug inhibits proteoglycan deposition, the present studies were undertaken to examine the chemical composition and tissue distribution of proteoglycans in order to determine, more precisely, their role during lung morphogenesis. Autoradiography of labeled 16- and 19-day embryonic lungs demonstrated greater incorporation over the mesenchyme. Treatment with beta-xyloside did not alter the autoradiographic appearance; however, beta-xyloside treatment followed by nitrous acid digestion, eliminated most silver grains. Isolation of proteoglycans from extracellular, membrane and intracellular pools over the 16- to 19-day interval demonstrated redistribution of heparan sulfate proteoglycan from an intracellular to a membrane location, while chondroitin sulfate proteoglycan redistributed from intracellular to extracellular. Only the synthesis of chondroitin sulfate proteoglycan was inhibited by beta-xyloside. On the basis of these results we suggest that a chondroitin sulfate proteoglycan is required for lung maturation and that inhibition of its synthesis results in inhibition of septa formation and subsequent failure of morphogenesis and differentiation.