Neural stem cells (NSCs) generate new hippocampal dentate granule neurons throughout adulthood. The genetic programs controlling neuronal differentiation of adult NSCs are only poorly understood. Here we show that, in the adult mouse hippocampus, expression of the SoxC transcription factors Sox4 and Sox11 is initiated around the time of neuronal commitment of adult NSCs and is maintained in immature neurons. Overexpression of Sox4 and Sox11 strongly promotes in vitro neurogenesis from adult NSCs, whereas ablation of Sox4/Sox11 prevents in vitro and in vivo neurogenesis from adult NSCs. Moreover, we demonstrate that SoxC transcription factors target the promoters of genes that are induced on neuronal differentiation of adult NSCs. Finally, we show that reprogramming of astroglia into neurons is dependent on the presence of SoxC factors. These data identify SoxC proteins as essential contributors to the genetic network controlling neuronal differentiation in adult neurogenesis and neuronal reprogramming of somatic cells.

Transplantation of Schwann cells (SCs) and olfactory ensheathing cells (OECs) have emerged as very promising therapies for spinal cord repair. The important features of interaction between SCs and OECs are beginning to be appreciated, although the underlying mechanism remains unclear. In the present study, we tested the effects of OECs on SCs migration using a range of in vitro migration assays. We found that SCs migrated abundantly upon OECs monolayer, and the migration-promoting effects were identified to be due to the secreted diffusible factors in OEC-derived conditioned medium (OEC-CM). Furthermore, neutralizing nerve growth factor (NGF) in OEC-CM with NGF antibody could block this effect. Moreover, we found that NGF promotes SCs migration even on astrocyte monolayer. Taken together, these findings provide the first evidence that OECs can promote SCs migration in astrocytic environment by secreted NGF.

Olfactory ensheathing cells (OECs) are the glial cells that derive from the olfactory placode, envelop olfactory axons in the course of migration from the olfactory epithelium to the olfactory bulb and reside primarily in the olfactory nerve layer. OECs transplantation as a promising experimental therapy for axonal injuries has been intensively studied; however, little is known about their roles in olfactory bulb development. In this study, we examined the effects of OECs on the migration of neural progenitors in rostral migratory stream (RMS). Initially, the neurosphere migration assay showed that OEC-conditioned medium promoted progenitors to migrate from RMS neurospheres in a concentration dependent manner. Moreover, co-culturing OECs nearby the RMS explants led to asymmetric migration of explants in different developing stages. However, OECs could influence the migration in a distance not further than 1.5 mm. Finally, slice assay that mimic the circumstance in vivo revealed that OECs had a chemoattractive activity on RMS neural progenitors. Together, these results demonstrate that OECs attract neural progenitors in RMS through the release of diffusible factors and it is likely that OECs mainly influence radial migration in the olfactory bulb but not tangential migration of the RMS invivo during development. This suggests a previously unknown function for OECs in olfactory development and a novel mechanism underlying the targeting of RMS cells.

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