Alterations in neural cell adhesion molecules during development of different regions of the nervous system

Several cell adhesion molecules involved in neuron-neuron and neuron- glia interactions have been identified in our laboratory and have been shown to undergo cell surface modulation. In the case of the neural cell adhesion molecule (N-CAM), it has been found that during development the molecule is converted from a microheterogeneous embryonic (E) form containing 30 gm of sialic acid/100 gm of polypeptide to several distinct adult (A) forms containing one third as much of this sugar. In vitro analyses indicate that this change is accompanied by a 4-fold increase in the rate of N-CAM homophilic binding. In the present study of the mouse and the chick, alterations of N-CAMs occurring as a result of E----A conversion, prevalence modulation, and changes in antigenic state during the development of different neural regions were analyzed by the use of highly specific polyclonal and monoclonal antibodies combined with anatomical dissection and several new quantitative assays. We made the following observations. The relative concentration of N-CAM changed during development, with the highest concentration (2.8 times the adult level) occurring around the perinatal period. Each brain region followed a similar pattern of change but according to a different time schedule. While conversion from the E to the A forms of N-CAM occurred mainly during the first 3 postnatal weeks in mice, the relative conversion rates were distinctly different in various neural tissues. The extreme examples are dorsal root ganglia, which already displayed the A forms at birth, and the diencephalon and tectal region, which still retained some E forms in the adult. A cephalocaudal maturation gradient of E---- A conversion was observed in the spinal cord and dorsal root ganglia. Differences in the antigenic determinants of N-CAMs from different neural tissues were detected by two independent monoclonal antibodies. Finally, in some adult neural tissues, one of the three A forms was found to be dominant. These results establish that during development there are definite quantitative and qualitative differences among N- CAMs from various neural tissues. The data are consistent with the hypothesis that alterations in the relative amounts and forms of N-CAM play major roles in neural morphogenesis, possibly by altering the rates of adhesion among neurons and their processes.