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. Author manuscript; available in PMC: 2010 May 26.
Published in final edited form as: Nat Rev Mol Cell Biol. 2008 Feb 20;9(4):285–296. doi: 10.1038/nrm2354

Figure 5. Multiple pathways responding to changes in O2 availability affect developmental processes as well as social behaviour.

Figure 5

As described in the text, HIFs regulate many aspects of cardiovascular morphogenesis and stem and/or progenitor cell maintenance. Mutagenesis of mammalian target of rapamycin (mTOR) and its associated proteins, such as raptor, rictor, and mLST8, has revealed an important role for mTORC1 and mTORC2 during embryonic development. However, whether mTOR is responding to hypoxia in embryonic microenvironments to regulate development remains to be determined. The “unfolded protein response” (UPR)-regulated kinase PERK (and its substrate eIF2α) is necessary for pancreatic β cell production during development or shortly after birth. Inositol-requiring-1 (IRE1) is another ER-associated UPR effector that activates X box-binding protein 1 (XBP-1), promoting the transcription of ER chaperone genes such as BiP and c/EBP-homologous protein (CHOP) 139. Finally, cyclic guanosine monophosphate (cGMP) regulation promotes neuronal activity and social feeding behaviour in C. elegans, allowing them to avoid O2 levels outside the range of 5–12% O2. This leads to specific appearances of nematode colonies, causing “bordering” or “aggregation”.