The functions of Npr3 during embryonic development

Natriuretic peptides and their receptors have been implicated in a broad range of physiological processes, regulating blood pressure, cardiac hypertrophy and fibrosis, fat metabolism, and long bone growth. They mediate their action through the modulation of intracellular levels of cGMP and cAMP. Here we report a completely novel function for natriuretic peptide signaling in the control of cell fate in the embryonic ectoderm. Using a combination of morpholino-based knockdowns, pharmacological inhibitors and rescue assays in Xenopus embryos we show that natriuretic peptide receptor 3 (Npr3), natriuretic peptide receptor 1 (Npr1) and the natriuretic peptide Nppc cooperate in the regulation of neural crest and cranial placode formation, two cell populations that make a major contribution to the craniofacial skeleton and paired sensory organs in vertebrates. Npr3 plays an especially pivotal role in this process by differentially regulating these two developmental programs. Our findings suggest that Npr3 has a dual function in the embryonic ectoderm, it (i) reduces ligand-mediated activation of Npr1 to generate cGMP levels compatible with neural crestformation, and (ii) modulates cAMP levels via inhibition of adenylyl cyclase to promote cranial placode fate. Therefore the intracellular modulation of these two-second messengers participates in the segregation of these cell populations during embryogenesis.