TISSUE-SPECIFIC AND DIFFERENTIAL EXPRESSION OF ALTERNATIVELY SPLICED ALPHA-1(II) COLLAGEN MESSENGER-RNAS IN EARLY HUMAN EMBRYOS

Expression of the alpha 1(II) procollagen gene is not confined to chon drogenic tissues during vertebrate development. Transcripts of the hum an gene (COL2A1) are alternatively spliced to give mRNAs which either exclude (type IIB mRNA) or include (type IIA mRNA) an exon encoding a cysteine-rich domain in the amino-propeptide. The distribution of COL2 A1 mRNAs in 27 to 44-day human embryos and 8- to 24-week fetuses was s tudied by in situ hybridization and RNase protection analyses. Type II A mRNAs were expressed in prechondrogenic cells and were also preferen tially expressed in chondrogenic tissues at regions of chondrocyte com mitment and cartilage growth. During maturation of chondrocytes, there is a switch to expression of type IIB mRNAs. In non-chondrogenic tiss ues of early embryos, type IIA mRNA expression was associated with act ive tissue remodeling, epithelial organization, and sites of tissue in teraction. Type IIA mRNAs were also expressed in some non-chondrogenic tissues where expression had previously been undetected, such as the tooth bud, liver, adrenal cortex, apical ectodermal ridge, and indiffe rent gonad. In older fetuses type IIA mRNAs were the sole or major tra nscript in most non-chondrogenic tissues except the choroid plexus and tendon. In the meninges there was a unique switch from type IIB to ty pe IIA expression. The expression pattern of COL2A1 transcripts sugges ts that, in addition to contributing to the structural integrity of th e cartilage extracellular matrix, type II procollagen may serve a morp hogenetic role in embryonic development. Our findings clearly show tha t the pattern of expression of type II procollagen mRNAs is largely co nserved between man and mouse. However, some differences exist, and th ese should be taken into consideration when animal models are used to study human diseases associated with COL2A1. (C) 1995 Wiley-Liss, Inc.