ORIGIN OF OLIGODENDROCYTES WITHIN THE HUMAN SPINAL-CORD

To determine the time and site of origin of the oligodendrocyte lineag e in the developing human spinal cord, we have examined tissues from 4 5 to 83 d postconception (dpc) using sets of probes and antibodies rec ognizing oligodendrocyte-specific glycolipids, transcripts, and protei ns. We found that two clusters of oligodendrocyte precursors appear on or before 45 dpc on each side of the cord ventral ependyma above the floor plate. These precursors express glycolipids recognized by the O4 and Rmab antibodies, platelet-derived growth factor alpha-receptor, m yelin basic protein (MBP), and 2',3'-cyclic nucleotide 3' phosphodiest erase as well as MBP and proteolipid transcripts. Expression of the mo rphogen sonic hedgehog was detected in the floor plate at 45 dpc and d ecreased at 58 dpc. During this period, oligodendrocyte precursors eme rged in the ventral and lateral region of the forming white matter, a process occurring first in cervical and later in lumbar cord. The majo rity of O4(+) cells express the proliferating cell nuclear antigen (PC NA), and their pattern of dispersion suggests that these cells progres sively populate the lateral and dorsal cord regions. Oligodendrocytes expressing galactocerebroside appeared at 53 dpc and did not express P CNA. Oligodendrocyte precursors were detected in dorsal cord regions a t 74 dpc and at 83 dpc when myelination started in the ventral roots. Thus, oligodendrocyte precursors expressing myelin transcripts and pro teins emerge in the ventral region of the embryonic cord several weeks before myelination.