Ectopic Expression of Olig1 Is Deleterious to V3 Interneuron Development in the Developing CNS

In the developing neural tube, precursors at defined positions along the dorsal-ventral axis respond to Sonic hedgehog (Shh) secreted from the notocord and floorplate and elaborate distinct neurons identified by homeodomain protein expression. Oligodendrocyte lineage genes (Olig1/2) that encode a novel class of bHLH proteins are expressed in the oligodendrocyte lineage in the CNS. Moreover, their early expression is regulated by Shh in a dosage-dependent manner, suggesting that Olig genes may play roles in pattern formation and neuronal and/or glial cell fate determination. To study possible Olig functions during development, we analyzed endogenous Olig1/2 expression and found that Olig genes were initially expressed in the mouse spinal cord as early as 8.5 dpc and that expression at 11.5 dpc occurred in a restricted domain. Olig expression overlaps Nkx2.2 expression, where V3 interneurons (INs) are generated. We next generated transgenic mice that ectopically express Olig1 in the ventricular zone under control of the Hoxb4 enhancer. Global disruption of pattern was not observed by analysis of markers for neural precursors (NPs), motor neurons, and V2 INs. In contrast, misexpression Oligl evidently is detrimental to production of V3 INs, as Sim1-expressing cells were absent in these transgenic mice. Moreover, increased levels of cell death were observed. These data suggest that Olig genes may antagonize the development of certain neuronal subtypes and may refine pattern formation in NPs of the ventral neural tube.