LAUSR

multiple oxygen-independent factors promoting HIF-1α stabilization. In cancer, the Warburg effect/pseudohypoxia, a state characterized for a change from aerobic to anaerobic metabolism, can promote HIF-1α stabilization through PHDs inhibition by 2oxoglutarate reduction. In neural crest cells (NCCs), Hif-1α regulates the epithelial-mesenchymal transition and chemotaxis. How this factor is stabilized in NCCs in vivo is poorly understood. It is known that a)NCCs exist under an epidermal cell layer and b)maximum oxygen exposure in NCC explants causes cells to behave normally, suggesting that Hif-1α is activated by an oxygen-independent mechanism. In our Lab we have seen that pdgf1a is one of the most overrepresented oxygen-independent factors present in zebrafish NCC. To test if pdgf1a regulates Hif-1α stabilization, pdgf1a fail-offunction, and rescue experiments were performed analyzing multiple Hif-1 targets. pdgf1a morpholino reduced Hif-1-activated genes, a reduction restored when co-injected with hif-1α mRNA. These data suggest that Pdgf1a regulates Hif-1α stabilization, but how NCC explants behave normally in absent from the Pdgf1a?. To address this question we hypothesized that when Hif-1α is stabilized it favors metabolic a switch from aerobic to anaerobic, a 2-oxoglutarate decrease and a positive feedback on its own stabilization. To test this we compared the expression levels of different Hif-1 targets related to the metabolic switch between pre migratory and migratory stage of the NCC and injected 2-oxoglutarate on pre migratory embryos observing neural crest migration, and Hif-1 targets related to this migration. Our data suggest that NCC change their metabolism and this cellular state can maintain their migration.