β-D-xylosides cause abnormalities of growth and development in chick embryos

Abstract

THE notion that the composition of the intercellular matrix plays an important part in vertebrate morphogenesis has received considerable indirect experimental support. At least four types of collagen are synthesised and secreted in different proportions by cells from various tissues¹, and many tissues have their own characteristic spectra of glycosaminoglycans, which undergo precise changes during development^2,3. Differentiation of several tissues and organs in vivo or in vitro is accompanied by major changes in collagen and glycosaminoglycans^4,5, and can even in some cases be promoted by addition of collagen^6,7 or glycosaminoglycans^8,9 to the culture medium. Direct evidence that the structure of collagen influences morphogenetic events is provided by studies in vivo with lathyrogens such as β-amino-propionitrile, which interefere with the crosslinking of collagen by inhibiting the action of the enzyme lysyl oxidase¹⁰. When administered to developing embryos or young animals, these agents produce a series of abnormalities including multiple bone deformations, vascular lesions and other manifestations of connective tissue damage¹¹. To date, there have been no similar studies of the role of chondroitin sulphate or other glycosaminoglycans in development, because no agent has been found that specifically affects the synthesis or structure of any proteoglycan in vivo. We report here that administration of β-D-xylosides to 9-d-old chick embryos leads to marked alterations in the structure of chondroitin sulphate and simultaneously causes reproducible changes in growth and morphology, which persist at least until the chick is ready to hatch. The morphological changes are unlike those associated with lathyrism.