Chondroitin sulfate proteoglycan synthesis and reutilization of β-d-xyloside-initiated chondroitin/dermatan sulfate glycosaminoglycans in fetal kidney branching morphogenesis

Branching morphogenesis and chondroitin sulfate proteoglycan synthesis by explanted fetal mouse kidneys were previously shown to be inhibited by p-nitrophenyl β-d-xylopyranoside (β-d-xyloside) while glomerular development and heparan sulfate proteoglycan synthesis were unaffected. The metabolic fate of fetal kidney explant proteoglycans was investigated to determine whether or not recovery of proteoglycan synthesis and morphogenesis occur after exposure to β-d-xyloside. Chondroitin sulfate proteoglycan synthesis resumed within 4 hr of removal of β-d-xyloside and was enhanced once β-d-xyloside-initiated chondroitin/dermatan-³⁵SO₄ glycosaminoglycans (GAGs) were released from the tissue. Radioactivity incorporated into β-d-xyloside-initiated chondroitin/dermatan-³⁵SO₄ GAGs during labeling in the presence of β-d-xyloside was reutilized in the synthesis of chondroitin-³⁵SO₄ proteoglycan during a 24-hr chase in nonradioactive medium without β-d-xyloside. Further, highly purified β-d-xyloside-initiated chondroitin/dermatan-³⁵SO₄ GAGs were taken up by kidneys more avidly than was free [³⁵S]sulfate. These ³⁵S-GAGs were degraded and reutilized in the synthesis of chondroitin-³⁵SO₄ proteoglycan. Ureteric bud branching resumed 48 hr after β-d-xyloside was removed from the incubation medium. These findings support the idea that both chondroitin sulfate proteoglycan synthesis and proteoglycan processing may be involved in branching morphogenesis.