Limb chondrogenesis is compromised in the versican deficient hdf mouse.

It has been suggested that the matrix proteoglycan, versican, may perform a functional role during early events of limb skeletogenesis largely by virtue of its spatiotemporal expression pattern in precartilage mesenchymal aggregations. The versican-deficient hdf transgenic mouse has provided the first model to explore the implications of a null mature versican on limb chondrogenesis. Due to lethality of hdf homozygous embryos prior to limb cartilage differentiation, high-density micromass cultures were employed to compare the chondrogenic capacity of hdf mutant limb mesenchyme to that of wild-type. In homozygous hdf mesenchyme, aggregation was severely compromised and neither cartilage-characteristic Type II collagen nor alcian blue positive foci were detected during a 6-day period of culture. Three-dimensional culture of hdf mutant mesenchyme, however, showed that in a permissive environment mutant cells also expressed Type II collagen. Results strongly suggest that mature versican proteoglycan is essential for precartilage aggregation and subsequent cartilage differentiation.