The oligodendrocyte myelin glycoprotein (OMgp) inhibits axon regeneration after injury in the adult mammalian central nervous system. However its function during brain development remains largely unknown. The present study aims to analyze a possible role for OMgp during neurogenesis. We showed that neural stem cells (NSC) extracted from the whole mesencephalon of rat embryos (E14) and cultured as free floating neurospheres expressed both OMgp and its receptor Nogo-R1. An over-expression of OMgp affected NSC expansion by reducing cell proliferation, but did not affect their differentiation into neurons. These findings indicate a new role for OMgp during brain development as a possible regulator of neurogenesis. Moreover, they suggest a possible implication for OMG gene in the etiology of neurofibromatosis type 1 forms characterized by a deletion of the NF1 gene locus containing OMG.