Molecular characterization of the TrkA/NGF receptor minimal enhancer reveals regulation by multiple cis elements to drive embryonic neuron expression

Neural development relies on stringent regulation of key genes that mediate specialized function. TrkA is primarily expressed in neural cres-derived sensory and sympathetic neurons where it transmits critical survival information. We have identified a 457 base pair sequencen upstream of the murine first TrkA coding exon that is conserved in human and in chick, and is sufficient for expression in the correct cells with appropriate timing. Mutation analysis of consensus transcription factor binding domains within the minimal enhancer reveals a complex positive regulation that includes sites required for global expresion and sites that are specifically required for DRG, trigeminal or sympathetic expression. These results provide a foundation for identification of the transcriptional machinery that specifies neurotrophin receptor expression.