Dorsal spinal cord inhibits oligodendrocyte development

Oligodendrocytes are the myelinating cells of the mammalian central nervous system. In the mouse spinal cord, oligodendrocytes are generated from stri ctly restricted regions of the ventral ventricular zone. To investigate how they originate from these specific regions, we used an explant culture sys tem of the E12 mouse cervical spinal cord and hindbrain. In this culture sy stem O4(+) cells were first detected along the ventral midline of the expla nt and were subsequently expanded to the dorsal region similar to in vivo. When we cultured the ventral and dorsal spinal cords separately, a robust i ncrease in the number of O4(+) cells was observed in the ventral fragment. The number of both progenitor cells and mature cells also increased in the ventral fragment. This phenomenon suggests the presence of inhibitory facto r for oligodendrocyte development from dorsal spinal cord. BMP4, a strong c andidate for this factor that is secreted from the dorsal spinal cord, did not affect oligodendrocyte development. Previous studies demonstrated that signals from the notochord and ventral spinal cord, such as sonic hedgehog and neuregulin, promote the ventral region-specific development of oligoden drocytes. Our present study demonstrates that the dorsal spinal cord negati vely regulates oligodendrocyte development. (C) 2000 Academic Press.