Asynchronous differentiation of clonally related spinal cord oligodendrocytes

Oligodendrocytes are responsible for myelination in the vertebrate central nervous system, but what controls their differentiation remains unknown. To determine if clonally related rat spinal cord oligodendrocyte precursors differentiated synchronously in a complex environment, retroviral clonal analysis was combined with immunocytochemistry using antibodies which define consecutive stages in oligodendrocyte development. In embryonic spinal cord cultures, most oligodendrocyte clones contained both differentiated oligodendrocytes and their precursors, demonstrating that clonally related oligodendrocytes differentiated asynchronously. Such asynchronous differentiation did not simply reflect differences in proliferation between clonally related cells. In young cultures, most clones were composed entirely of dividing cells. In older cultures, most clones contained nonproliferating immature precursor cells, suggesting that oligodendrocyte proliferation and differentiation are independently regulated, and differentiation is primarily regulated by environmental factors.