Developmentally regulated alternative splicing of the alpha 1(XI) collagenchain: Spatial and temporal segregation of isoforms in the cartilage of fetal rat long bones
Np. Morris et al., Developmentally regulated alternative splicing of the alpha 1(XI) collagenchain: Spatial and temporal segregation of isoforms in the cartilage of fetal rat long bones, J HIST CYTO, 48(6), 2000, pp. 725-741
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.