ON-DEMAND INDUCTION OF SECRETAGOGIN EXPRESSION REGULATES NEUROBLAST MIGRATION AND CORTICAL REGENERATION

Tens of thousands of newly born cells migrate along the rostral migratory stream to reach their target, the olfactory bulb. We previously identified a neuronal population in this pathway which releases a matrix-degrading enzyme to dismantle the extracellular matrix, thereby facilitating neuroblast migration. This mechanism is activity dependent and is regulated by the calcium-sensor protein secretagogin. Here, we show that neuroblasts can leave the migratory stream and find an alternative route toward the prefrontal cortex. We labelled newly born neuroblasts with BrdU and found that their path was lined by secretagogin-expressing neurons, similar to the organization of the rostral migratory stream. These secretagogin- positive neurons were stationary but retained the capacity to migrate, and their number increased upon system activation. Of note, secretagogin neurons received direct contacts from the prefrontal cortex, and increased cortical activity enhanced neuroblast migration towards the prefrontal cortex. Lesion of the prefrontal cortex increased the number of neuroblasts that migrate
toward the lesioned cortex, whereas the number of neuroblasts moving toward the olfactory bulb remained unchanged. Adult cortex typically lacks secretagogin- expressing neurons. Nevertheless, secretagogin-expressing cells appeared in the penumbra as well as along the route leading to the injured area. These secretagogin-expressing cells were neither migrating neuroblasts, nor astrocytes, nor microglia. They were closely associated with BrdU-labelled neurons, suggesting a role in guiding them toward their destination, the penumbra region. We suggest that secretagogin is expressed in an on-demand manner following brain injury and contributes to shaping regenerative processes.