EXPRESSION OF THE NEURAL AXON ADHESION MOLECULE L1 IN THE DEVELOPING AND ADULT-RAT BRAIN

L1 is a developmentally regulated adhesion molecule that may play a ro le in some aspects of axonal guidance. With Northern blots we find pea k expression of L1 RNA at postnatal day 1 (P1) in the developing rat b rain. Western blots show a peak of protein on P15. The major form of L 1 is 200 kDa, but lower molecular mass forms are found including 140 a nd 80 kDa, representing, respectively, the extracellular and intracell ular regions of L1. Ah molecular mass forms of L1 change during develo pment. Although expressed at lower levels than during development, L1 is found in all brain regions in the adult rat. Different regions of t he brain show differential expression and regulation of L1 and its pep tide fragments. For instance, the hypothalamus showed an enhanced L1-8 0/L1-200 ratio at P10 and P15 relative to that expressed by cerebellum and hippocampus. Cerebellar granule cells in culture showed strong L1 -200 and almost no L1-60, 80, or -140, in contrast to the intact cereb ellum at the same age, which showed weaker L1-200 and strong L1-60, -8 0, and -140. Control experiments indicated that the L1 proteolytic cle avage found in different developing brain regions occurred in vivo and was not a result of sample preparation. The amount of L1-200 in cultu red granule cells was proportional to the measured length of the growi ng axon. Neuronal activity (increased with 25 mM K+, 100 mu m N-methyl -D-aspartate, and 100 mu m 4-aminopyridine) enhanced L1 transcription and translation. Together, these data suggest differential regulation of L1 expression and proteolytic cleavage specific for developmental a ges and brain regions.