The hormone erythropoietin (EPO) has therapeutic potential due to its neuroprotective effects and because it is induced following hypoxia or injury. Although EPO and its receptor EPOR are expressed in the developing mammalian brain, the role of EPO signalling during corticogenesis is not well understood. Now, Jozsef Kiss and colleagues show that EPO signalling regulates the radial migration of cortical neurons in the rat cerebral cortex. Using short-hairpin RNA (shRNA) transient knockdown of EPOR, the researchers demonstrate that the laminar positioning of excitatory neurons is affected in EPOR-deficient conditions, with fewer neurons reaching the cortical plate. They reveal through live imaging that EPOR loss-of-function reduces neuronal migration speed and affects neuronal transition to a migratory (bipolar) state. ERK overexpression rescues migration in EPOR knockdown cells, indicating that it functions downstream of EPO signalling. Moreover, EPO upregulation affects neuronal migration but not bipolar transition. Transient knockdown of EPOR in prenatal rat brains has permanent consequences with neuronal differentiation, synapse formation and neuron localisation affected in adult brains. In addition, neuronal activation, circuit formation and behaviour are affected in adults, all of which can be rescued by ERK overexpression. Together, these results demonstrate a crucial role for EPO signalling in neuronal migration.
Erythropoietin instructs neuronal migration
Erythropoietin instructs neuronal migration. Development 1 October 2020; 147 (19): e1902. doi:
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