Cyclic AMP signaling functions as a bimodal switch in sympathoadrenal celldevelopment in cultured primary neural crest cells

Cells of the vertebrate neural crest (crest cells) are an invaluable model system to address cell fate specification. Crest cells are amenable to tiss ue culture, and they differentiate to a variety of neuronal and nonneuronal cell types, Earlier studies have determined that bone morphogenetic protei ns (BMP-2. -4, and -7) and agents that elevate intracellular cyclic AMP (cA MP) stimulate the development of the sympathoadrenal (SA, adrenergic) linea ge in neural crest cultures. To investigate whether interactive mechanisms between signaling pathways influence crest cell differentiation, we charact erized the combinatorial effects of BMP-2 and cAMP-elevating agents on the development of quail trunk neural crest cells in primary culture, We report that the cAMP signaling pathway modulates both positive and negative signa ls influencing the development of SA cells. Specifically, ne show that mode rate activation of cAMP signaling promotes, in synergy with BMP-2, SA cell development and the expression of the SA lineage-determining gene Phox2a. B y contrast, robust activation of cAMP signaling opposes, even in the presen ce of BMP-2, SA cell development and the expression of the SA lineage-deter mining ASH-1 and Phox2 genes. We conclude that cAMP signaling acts as a bim odal regulator of SA cell development in neural crest cultures.