Developmentally regulated alternative splicing of the alpha1(XI) collagen chain: 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 fetal cartilage and is required to maintain the unusually thin diameter of these fibrils. The mature matrix form of the molecule retains an N-terminal variable region whose structure is modulated by alternative exon splicing that is tissue-specific and developmentally regulated. In the alpha1(XI) chain, antibodies to two of the peptides, p6b and p8, encoded by the alternatively spliced exons localized these epitopes to the surface of the collagen fibrils and were used to determine the pattern of isoform expression during the development of rat long bones (humerus). Expression of the p6b isoform was restricted to the periphery of the cartilage underlying the perichondrium 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 differentiation and were detected throughout prechondrogenic mesenchyme and immature cartilage. After E16, p8 isoforms gradually disappeared from the diaphysis and then from the epiphysis preceding chondrocyte hypertrophy, but were highly evident at the periarticular joint surface, where ongoing chondrogenesis accompanies the formation of articular cartilage. The spatially restricted and differentiation-specific distribution of alpha1(XI) isoforms is evidence that Type XI collagen participates in skeletal development via a mechanism that may be distinct from regulation of fibrillogenesis.
Morris
N P
NP
Research Department, Shriners Hospital for Children, Portland, OR 97201, USA. npm@shcc.org
Oxford
J T
JT
Davies
G B
GB
Smoody
B F
BF
Keene
D R
DR
D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D000906:Antibodies / Q000276:immunology; D002358:Cartilage, Articular / Q000196:embryology* / Q000648:ultrastructure; D003094:Collagen / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006811:Humerus / Q000196:embryology* / Q000648:ultrastructure; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D051381:Rats
D000906:Antibodies; D020033:Protein Isoforms; D003094:Collagen