Developmentally regulated alternative splicing of the alpha 1(XI) collagenchain: Spatial and temporal segregation of isoforms in the cartilage of fetal rat long bones

Type XI collagen is a component of the heterotypic collagen fibrils of feta l cartilage and is required to maintain the unusually thin diameter of thes e fibrils. The mature matrix form of the molecule retains an N-terminal var iable region whose structure is modulated by alternative exon splicing that is tissue-specific and developmentally regulated. In the alpha 1(XI) chain , antibodies to two of the peptides, p6b and p8, encoded by the alternative ly spliced exons localized these epitopes to the surface of the collagen fi brils and were used to determine the pattern of isoform expression during t he development of rat long bones (humerus). Expression of the p6b isoform w as restricted to the periphery of the cartilage underlying the perichondriu m of the diaphysis, a pattern that appears de novo at embryonic Day (E) 14. P8 isoforms appeared to be associated with early stages of chondrocyte dif ferentiation and were detected throughout prechondrogenic mesenchyme and im mature cartilage. After E16, p8 isoforms gradually disappeared from the dia physis and then from the epiphysis preceding chondrocyte hypertrophy, but were highly evident at the periarticular joint surface, where ongoing chond rogenesis accompanies the formation of articular cartilage. The spatially r estricted and differentiation-specific distribution of alpha 1(XI) isoforms is evidence that Type XI collagen participates in skeletal development via a mechanism that may be distinct from regulation of fibrillogenesis.