Hypoxia-Responsive Subtype Cells Differentiate Into Neurons in the Brain of Zebrafish Embryos Exposed to Hypoxic Stress

Severe hypoxia results in complete loss of central nervous system (CNS) function in mammals, while several other vertebrates, such as zebrafish, can regenerate after hypoxia-induced injury of CNS. Since the cellular mechanism involved in this remarkable feature of other vertebrates is still unclear, we studied the cellular regeneration of zebrafish brain, employing zebrafish embryos from transgenic line huORFZ exposed to hypoxia and then oxygen recovery. GFP-expressing cells, identified in some cells of the CNS, including some brain cells, were termed as hypoxia-responsive recovering cells (HrRCs). After hypoxia, HrRCs did not undergo apoptosis, while most non-GFP-expressing cells, including neurons, did. Major cell types of HrRCs found in the brain of zebrafish embryos induced by hypoxic stress were neural stem/progenitor cells (NSPCs) and radial glia cells (RGs), that is, subtypes of NSPCs (NSPCs-HrRCs) and RGs (RGs-HrRCs) that were induced by and sensitively responded to hypoxic stress. Interestingly, among HrRCs, subtypes of NSPCs- or RGs-HrRCs could proliferate and differentiate into early neurons during oxygen recovery, suggesting that these subtype cells might play a critical role in brain regeneration of zebrafish embryos after hypoxic stress.