NEURAL SELECTIVE ACTIVATION AND TEMPORAL REGULATION OF A MAMMALIAN GAP-43 PROMOTER IN ZEBRAFISH

Neurons throughout the vertebrate nervous system selectively activate the gene for a growth cone component, GAP-43, during embryonic develop ment, and then decrease its expression abruptly as they form synapses. Distal interruption of mature axons in the central nervous system (CN S) of fish and amphibians, but not in the mammalian CNS reverses the d evelopmental down-regulation of GAP-43 expression. To explore function al conservation and divergence of cis-acting elements that regulate ex pression of the GAP-43 gene, we studied activation, in transgenic zebr afish embryos, of mammalian GAP-43 genomic sequences fused to a marker gene. The DNA fragments containing the GAP-43 promoter, including a s hort fragment of 386 base pairs, were preferentially activated in the embryonic fish nervous system at times when extensive neuronal differe ntiation and neurite outgrowth take place. After 2 days of development , expression of the mammalian transgenes was specifically downregulate d in the fish spinal cord but increased in more rostral regions of the CNS. This expression pattern was well correlated with the regulation of the endogenous fish GAP-43 gene revealed by in situ hybridization. Elements of the mammalian gene located a substantial distance upstream of the minimal promoter directed additional expression of the marker gene in a specific set of non-neural cells in zebrafish embryos. Our r esults indicate that cis-acting elements of the GAP-43 gene, and signa ling pathways controlling these elements during embryonic development, have been functionally conserved in vertebrate evolution.