Differential regulation of transcription factor gene expression and phenotypic markers in developing sympathetic neurons

Abstract

We have examined the regulation of transcription factor gene expression and phenotypic markers in developing chick sympathetic neurons. Sympathetic progenitor cells first express the bHLH transcriptional regulator 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 detected one stage later, followed by the catecholaminergic neurotransmitter enzyme tyrosine hydroxylase (TH). We have used these markers to ask two questions: (1) is their expression dependent upon inductive signals derived from the notochord or floor plate?; (2) does their sequential expression reflect a single linear pathway or multiple parallel pathways? Notochord ablation experiments indicate that the floor plate is essential for induction of GATA-2, Phox2 and TH, but not for that of Cash-1 and SCG10. Taken together these data suggest that the development 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 properties. The parallel specification of different components of the terminal neuronal phenotype is likely to be a general feature of neuronal development.

The sympathies of the body: functional organization and neuronal differentiation in the peripheral sympathetic nervous system

“…Growth factors critically involved in this inductive process are bone morphogenetic proteins 4 and 7 that become expressed in the wall of the developing aorta (Reissmann et al 1996 ; Shah et al 1996 ; Schneider et al 1999 ). In addition, a notochord-derived signal was found important in early experiments in the chick embryo (Groves et al 1995 ). Importantly, BMPs and notochord-derived sonic hedgehog have shown to be instrumental in the differentiation of sympathetic neurons from human pluripotent stem cells (Huang et al 2016 ; Oh et al 2016 ; Frith and Tsakiridis 2019 ).…”