Developmental regulation of alternative splicing in the mRNA encoding Xenopus laevis neural cell adhesion molecule...

The neural cell adhesion molecule (NCAM) is thought to play a role in the formation of the vertebrate nervous system. In mammals and chicken, it is known that more than 100 different forms of the NCAM protein can be generated by alternative splicing of one primary transcript and it is possible that these different forms have distinct biological functions. A large part of the diversity is generated by alternative mRNA splicing in two regions, called the pi and the muscle specific domain (MSD), that encode portions of the extracellular domain of the NCAM protein. In this report, we describe the tissue and developmental expression of the pi and MSD sequences in the amphibian, Xenopus laevis. Our experiments show that NCAM transcripts are present in all tissues examined including muscle, heart, liver, kidney, and brain. We have identified a 30-base exon, similar to the pi domain observed in mammals, that is not present in maternal NCAM RNA but appears in a subset of the NCAM mRNA population shortly after neural induction. At the predicted location of the MSD we have detected only two alternatively spliced exons, 3 bases and 15 bases in length. In no X. laevis tissue examined did we detect the two additional alternatively spliced exons which are present in the MSD region of mammalian and chicken NCAM RNAs. Finally, the analysis has revealed a dynamic and complex pattern of expression of alternatively spliced NCAM mRNAs during embryogenesis. High levels of expression of specific forms of NCAM RNA correlate with major morphogenic events such as neural tube formation and metamorphosis.