Noggin upregulates Fos expression by a calcium-mediated pathway in amphibian embryos.

In amphibia, noggin, one of the neural inducers expressed in the Spemann organizer, acts by neutralizing the effects of bone morphogenetic protein-4 (BMP-4). It is shown that noggin is able to activate L-type calcium channels. The fos proto-oncogene is known to be induced within minutes by calcium signaling. Here it is reported that in animal cap explants of the amphibian Pleurodeles waltl, noggin can induce upregulation of a FOS-related protein in a calcium-dependent manner. Specific inhibition of the dihydropyridine sensitive L-type calcium channels blocked both calcium influx and the induction of FOS-related protein. When animal cap explants were treated with caffeine in order to release calcium from an internal store or with a specific agonist of the L-type calcium channels, FOS-related protein could be detected in cell nuclei by 5 or 15 min, respectively. Additionally, the calcium calmodulin kinase inhibitor. KN62, could block the upregulation of FOS-related protein induced by agents that increased intracellular calcium ([Ca2+]i). The present results suggest that transcription factors from the FOS family are downstream targets of neural inducer noggin.