A new study published in Development by Mekki-Dauriac et al. shows that bone morphogenetic proteins (BMPs) are negative regulators of oligodendrocyte precursor specification in the spinal cord. Although such a role for BMPs had been proposed on the basis of previous in vitro experiments, the new data provide solid evidence for the involvement of these proteins in oligodendroglial development in vivo.
In the embryonic spinal cord, oligodendrocyte precursors are localized to a ventral domain that expresses Nkx2.2 and Olig2, two transcription factors that are essential for oligodendroglial development. The morphogenic protein sonic hedgehog (Shh) induces precursor specification and the expression of these transcription factors. By contrast, the dorsal spinal cord, an important source of BMPs, lacks oligodendrocyte precursors, raising the possibility that these proteins have a negative influence on the specification of precursor cells. By applying BMP4 to ventral cord explants, or by grafting BMP2-producing cells into the developing spinal cord, the authors were able to inhibit oligodendrocyte development. In addition, ablation of the dorsal cord or transplantation of cells that produced noggin (a BMP-signalling inhibitor) had the opposite effect: an increase in the number of oligodendrocyte precursors.
Mekki-Dauriac et al. found that BMP4 repressed the expression of Olig2, but not of Nkx2.2, indicating that BMPs might exert their inhibitory effect by directly antagonizing some of the effects of Shh. So, as is the case for other cell populations in the spinal cord, a fine balance between the opposing actions of BMPs and Shh controls the specification of oligodendrocyte precursors.
ORIGINAL RESEARCH PAPER
Mekki-Dauriac, S. et al. Bone morphogenetic proteins control oligodendrocyte precursor specification in the spinal cord. Development 129, 5117–5130 (2002)
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López, J. BuMPing oligodendrocytes in the cord. Nat Rev Neurosci 3, 918 (2002). https://doi.org/10.1038/nrn1000
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DOI: https://doi.org/10.1038/nrn1000