DIFFERENTIAL REGULATION OF TRANSCRIPTION FACTOR GENE-EXPRESSION AND PHENOTYPIC MARKERS IN DEVELOPING SYMPATHETIC NEURONS

We have examined the regulation of transcription factor gene expressio n and phenotypic markers in developing chick sympathetic neurons. Symp athetic progenitor cells first express the bHLH transcriptional regula tor Cash-1 (a chicken achaete-scute homologue), followed by coordinate expression of Phox2, a paired homeodomain protein, and GATA-2, a zinc finger protein. SCG10, a pan-neuronal membrane protein, is first dete cted one stage later, followed by the catecholaminergic neurotransmitt er enzyme tyrosine hydroxylase (TH). We have used these markers to ask two questions: (1) is their expression dependent upon inductive signa ls derived from the notochord or floor plate?; (2) does their sequenti al expression reflect a single linear pathway or multiple parallel pat hways? Notochord ablation experiments indicate that the floor plate is essential for induction of GATA-2 Phox2 and TH, but not for that of C ash-1 and SCG10. Taken together these data suggest that the developmen t of sympathetic neurons involves multiple transcriptional regulatory cascades: one, dependent upon notochord or floor plate-derived signals and involving Phox2 and GATA-2, is assigned to the expression of the neurotransmitter phenotype; the other, independent of such signals and involving Cash-1, is assigned to the expression of pan-neuronal prope rties. The parallel specification of different components of the termi nal neuronal phenotype is likely to be a general feature of neuronal d evelopment.