Expression of NCAM isoforms during skeletal myogenesis in the mouse embryo

Abstract

We have examined the developmental patterns of neural cell adhesion molecule (NCAM) gene expression in embryonic mouse skeletal muscle cells by in situ hybridization. Moreover, by utilising exon-specific cRNA probes, we have examined tissue specific splicing of the NCAM gene. We show that there is a distinct sequence of NCAM isoform expression during skeletal muscle development. Since NCAMs are also expressed in other cell types, particularly neurons, NCAM mRNAs have been colocalised with acetylcholine receptor a (AChRa) gene transcripts to identify muscle-specific expression. NCAM is first detected in somites as they first form, prior to their differentiation into muscle and nonmuscle compartments. Myotomes, the first skeletal muscle masses to form in the embryo, express mRNAs for the transmembrane 180 and 140 kDa isoforms of NCAM. Both of these transcripts are also detected in the neural tube, and their spatial pattern of expression changes with development. Transcripts containing the muscle-specific domain (MSD) of the NCAM gene are not detected prior to 11 days postcoitum (p.c.1, at a time when rostra1 somites already contain well-developed myotomes. As the level of MSD mRNAs increases at 12 days P.c., the 140 and 180 kDa transcript levels decrease in skeletal muscle masses. The level of all NCAM isoform transcripts declines between 13 and 15 days p.c. in muscle. However, the 180 and 140 kDa NCAM isoforms are expressed at a high level in neural tissue and in other locations in the developing embryo such as in smooth muscle, around vibrissae follicles, and in the perichondrial zone of digits. o 1992 Wiley-Liss, Inc.

Close encounters: regulation of vertebrate skeletal myogenesis by cell-cell contact

“…NCAM exists as multiple polypeptides that arise from alternative splicing and can include a muscle-specific domain (MSD) between the FNIII repeats that is a site of O-linked glycosylation (Lyons et al, 1992). In mice, NCAM mRNA is expressed in epithelial somites and throughout myogenesis; during this process, specific isoforms display dynamic changes in their expression levels (Lyons et al, 1992).…”

“…NCAM exists as multiple polypeptides that arise from alternative splicing and can include a muscle-specific domain (MSD) between the FNIII repeats that is a site of O-linked glycosylation (Lyons et al, 1992). In mice, NCAM mRNA is expressed in epithelial somites and throughout myogenesis; during this process, specific isoforms display dynamic changes in their expression levels (Lyons et al, 1992). Overexpression of specific isoforms of NCAM in C2 myoblasts enhances cell-cycle withdrawal, creatine kinase activity and the rate of myoblast fusion (Dickson et al, 1990;Peck and Walsh, 1993); furthermore, mice expressing an NCAM-encoding transgene display enhanced secondary myoblast fusion (Fazeli et al, 1996).…”

Transcriptional down-regulation of myogenin expression is associated with v-ras-induced block of differentiation in unestablished quail muscle cells

“…Experimental evidence indicates that proper functioning of MRFs such as MyoD, myf5, myogenin and MRF4 and of their positive (E12/E47) and negative (Id) coregulators is required for myogenic dierentiation (Benezra et al, 1990;Lassar et al, 1991;Lyons and Buckingham, 1992). In order to understand why dierentiation was blocked in QM(ras), we have analysed the pattern of expression of these genes in cells grown in GM or DM, with the exception of the MRF4 homologue, that is not expressed in cultured quail muscle cells, and of E2A, whose expression showed no substantial dierences between normal and transformed quail myoblasts (unpublished observations).…”

Neural cell adhesion molecule (NCAM) marks adult myogenic cells committed to differentiation

“…In muscle, NCAM exists in multiple isoforms, which arise from alternative splicing of a single gene [67,68]. NCAM is also subject to several forms of post-translational modification: polysialylation of residues in the immunoglobulin domains is commonly found during development and has recently been shown to increase membrane repulsion and to enhance directional migration in specific cell types [69,70].…”