The early amniote embryo develops in a hypoxic environment: until blood circulation commences, oxygen availability in the developing tissues is low. What consequences does this have for development? On p. , Nobue Itasaki and co-workers investigate the role of the hypoxia-responsive HIF pathway in regulating cranial neural crest cell (CNCC) production in the chick – which normally occurs in a hypoxic environment. They find that, upon embryo culture under normoxia, fewer CNCCs emerge from the neural tube; this phenotype can be rescued upon drug-induced activation of the HIF-1α pathway. Consistent with this, the authors observe reduced expression of known markers and regulators of migratory neural crest – several of which have previously been implicated as HIF-1α targets. It therefore appears that hypoxia is necessary for normal CNCC production, but is it sufficient to induce ectopic CNCCs? Activation of HIF-1α at later stages, after blood circulation has normally commenced, can induce CNCC production in in vitro explants, though only weak effects are seen in embryos. These data highlight the importance of the hypoxic environment for normal cranial development and imply that the initiation of blood circulation might have broad developmental consequences related to oxygen availability and HIF signalling.
