Semaphorin7a regulates proliferation of newly- born neuron in the subventricular zone - olfactory bulb system of adult mice

In the adult mammalian brain, new neurons are continuously born and functionally integrated into the hippocampus and olfactory bulb. In rodents, integration of new inhibitory interneurons in the main (MOB) and accessory (AOB) olfactory bulb is essential for odor learning and mate recognition and is modulated by experience. Newborn interneurons originate in the subventricular zone (SVZ) and in the rostral migratory stream (RMS), from heterogeneous stem/progenitor cells whose dynamic is controlled by a complex network of cellular and molecular interactions still largely unknown. Here, we investigated the role of GPI-linked semaphorin Semaphorin7A (Sema7A) in this system. In situ hybridization and RT-PCR on SVZ-derived selected progenitor cells show that Sema7A and its receptors plexinC1 and beta1-integrin are expressed in the SVZ and RMS, in a partially overlapping pattern. A time-course analysis on the dynamic of BrdU-positive newborn cells in Sema7A KO compared to wild type mice, reveals an increase in BrdU-positive cells at short survival time (3 and 7 days), and no differences at longer survival time (15 and 28 days). Thus, lack of Sema7A influences progenitor proliferation, with no effects on newborn cell integration/survival. Similar results obtained on plexinC1 KO mice indicate this receptor as a strong candidate to mediate Sema7A function in the control of adult progenitor proliferation. Notably, the effect observed in Sema7A and plexinC1 KO mice is spatially defined, beeing mostly confined to the RMS and AOB, suggesting that Sema7A-plexinC1 interaction might act selectively on AOB interneuron progenitors. In line with this hypothesis, pheromonal odor exposure on Sema7A KO mice results in enhanced integration/survival of AOB newborn neurons, indicating a possible role for Sema7A in the control of activity-driven AOB neurogenesis.