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

David J. Klein, David M. Brown, Antoinette Moran, Theodore R. Oegema, Jeffrey L. Platt

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)515-528
Number of pages14
JournalDevelopmental Biology
Volume133
Issue number2
DOIs
StatePublished - Jun 1989

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