DEVELOPMENTAL-CHANGES IN EPITOPE ACCESSIBILITY AS AN INDICATOR OF MULTIPLE STATES OF AN IMMUNOGLOBULIN-LIKE NEURAL CELL-ADHESION MOLECULE

Cell surface molecules with restricted spatial and temporal distributi ons are good candidates for mediators of the cell-cell interactions th at are necessary for the development of the nervous system. A monoclon al antibody (MAb 23A7) was produced that selectively and transiently l abeled a limited subset of axons in the chick embryo spinal cord. Dete rmination of the N-terminal amino acid sequence and immunoprecipitatio n experiments demonstrated that the 23A7 antigen is identical to Bravo /Nr-CAM, a previously described cell adhesion molecule with immunoglob ulin-like domains (E.J. de la Rosa, J.F. Kayyem, J.M. Roman, Y.-D. Sti erhof, W.J. Dreyer, and U. Schwartz [1989] J. Cell Biol. 111:3087-3096 ; M. Grumet, V. Mauro, M.P. Goon, G.M. Edelman, and B.A. Cunningham [1 991] J. Cell Biol. 113:1399-1412). The temporal distribution of the 23 A7 antigen is unusual in that, immunohistochemically, MAb 23A7 binding greatly decreases after 7 days of development, whereas Western blot a nalysis indicates increasing levels of the antigen until 17 days of de velopment. In contrast, an antiserum against purified Nr-CAM, which al so binds only to the 2387 antigen, labels nearly all the axons in the tissue throughout all the later stages of development. These anomalous observations are apparently not the result of differential sensitivit y of the 23A7 epitope to fixation, the use of suboptimal concentration s of the MAb, or selective MAb binding to a subset of Bravo/Nr-CAM mol ecules produced by alternative splicing of the transcript or by posttr anslational modification. These findings could indicate the existence of multiple states of Bravo/Nr-CAM, which during development, vary in the accessibility of their extracellular domains to the MAb. This sugg ests the existence of multiple conformation or aggregation states of t his cell adhesion molecule, each of which might be performing a differ ent function. (C) 1995 Wiley-Liss, Inc.