Crest-derived precursors are induced to give rise to the progenitors of the SNS. This induction results in the independent activation of Phox2b and Mash1. The function of Mash1 remains unclear but it appears to promote the survival of neuronal progenitors and possibly also, their differentiation. Phox2b expression is required for Gata2, Gata3, Hand2, and the genes encoding TH and DBH to be expressed. The regulation of Th and Dbh requires the interaction of Phox2b, Hand2 and Gata3 and the loss of these factors leads to the absence of, or a substantial reduction in the number of neurons expressing a noradrenergic phenotype. Hand2 is essential for Hand1 expression with the role of Hand1 remaining unknown.