Spatiotemporal expression of two cell-cell adhesion molecule 105 isoforms during liver development

The rat liver adhesion molecule cell CAM 105 has been postulated to be involved in liver histogenesis. Recently, it was shown to exist in two isoforms that differ in the length of their cytoplasmic domains (O. Culic, Q-H. Huang, D. Flanagan, D. C. Hixson, and S. H. Lin, Biochem. J., 285: 47-53, 1992). Isoform-specific differences in phosphorylation and aggregation function have been observed. To study the possible roles of these isoforms during liver development, we have used both complementary DNA probes and isoform-specific antibodies to examine their temporal and spatial expression. Northern blot analysis revealed low steady-state levels of a 4.0-kilobase RNA at 15-20 days gestation, which increased dramatically at birth and remained at least 12-fold higher than fetal levels in neonatal and adult liver. Additional polyadenylated RNA species of 6.0 and 2.9 kilobases were detected after birth. Steady-state levels of cell CAM 105 RNA in cultured adult and fetal hepatocytes were comparable to in vivo levels, respectively, and were not influenced by treatment with transforming growth factor beta or by culture density. Increases in cell CAM 105 protein demonstrated by immunoblot analysis correlated with the RNA increases, suggesting that regulation of cell CAM 105 expression is largely transcriptional during development. Ratios of the long and short isoforms remained relatively constant after birth. Isoform-specific antipeptide antibodies localized both isoforms primarily to maturing bile canalicular domains of hepatocytes during liver development. The long isoform could not be detected in fetal liver in situ prior to 20 days, however, suggesting that specific roles may exist for these molecules during development.