Bone morphogenetic proteins negatively control oligodendrocyte precursor specification in the chick spinal cord.

Abstract

In the vertebrate spinal cord, oligodendrocytes originate from a restricted region of the ventral neuroepithelium. This ventral localisation of oligodendrocyte precursors (OLPs) depends on the inductive influence of sonic hedgehog (Shh) secreted by ventral midline cells. We have investigated whether the ventral restriction of OLP specification might also depend on inhibiting signals mediated by bone morphogenetic proteins (BMPs). BMPs invariably and markedly inhibited oligodendrocyte development in ventral neural tissue both in vitro and in vivo. Conversely, in vivo ablation of the dorsal most part of the chick spinal cord or inactivation of BMP signalling using grafts of noggin-producing cells promoted the appearance of neuroepithelial OLPs dorsal to their normal domain of emergence, showing that endogenous BMPs contribute to the inhibition of oligodendrocyte development in the spinal cord. BMPs were able to oppose the Shh-mediated induction of OLPs in spinal cord neuroepithelial explants dissected before oligodendrocyte induction, suggesting that BMPs may repress OLP specification by interfering with Shh signalling in vivo. Strikingly, among the transcription factors involved in OLP specification, BMP treatment strongly inhibited the expression of Olig2 but not of Nkx2.2, suggesting that BMP-mediated inhibition of oligodendrogenesis is controlled through the repression of the former transcription factor. Altogether, our data show that oligodendrogenesis is not only regulated by ventral inductive signals such as Shh, but also by dorsal inhibiting signals including BMP factors. They suggest that the dorsoventral position of OLPs depends on a tightly regulated balance between Shh and BMP activities.