In zebrafish, spinal cord oligodendrocytes originate in the ventral neural tube (Brosamle and Halpern,2002; Shin et al.,2003). olig2-expressing cells in the neural tube and hindbrain define motor neuron/oligodendrocyte progenitors, cells that give rise to motor neurons and oligodendrocytes (Park et al.,2002; Shin et al.,2003). In contrast to olig2, which is already strongly expressed before 20 hr post-fertilization (hpf), olig1 expression was first detected at 36 hpf medially in the midbrain, in a region that also expressed olig2 and sox10 (Fig. 2A,C, red arrowhead). Hindbrain expression of olig1 and sox10 also started by 36 hpf (Fig. 2A, yellow arrowhead; Fig. 2D, red arrowhead). By 48 hpf, expression of olig1 increased significantly and was detected in the fore-, mid-, and hindbrain (Fig. 2A,C,D). olig1-, olig2-, and sox10-positive oligodendrocytes appear to rapidly spread and populate the brain between 36–48 hpf. The midbrain expression of all three markers has shifted laterally away from the initial medial onset (Fig. 2A,C, red arrowheads). At later stages, when mbp starts to be expressed in differentiated oligodendrocytes and Schwann cells, olig1 and olig2 remain expressed widely throughout the brain (Fig. 2B: 72, 96, and 120 hpf). When compared to olig2, olig1 is only expressed in individual cells of the anterior spinal cord by 48 hpf (Supp. Fig. 1B, which is available online).
Figure 2. olig1 expression specifically marks differentiating oligodendrocytes. A: Onset of olig1 expression at 36 hpf in the brain was delayed compared to olig2 expression (from 22 hpf). Red arrowheads indicate midbrain oligodendrocytes characterized by olig1, olig2, and sox10 expression. Yellow arrowheads indicate earliest expression of olig1, olig2, and sox10 in hindbrain oligodendrocytes. Red brackets mark hindbrain expression of olig1 and olig2 at 48 hpf. Red asterisks indicate cerebellum expression of olig2. B: During late stages of embryogenesis, olig1- and olig2-expressing oligodendrocytes rapidly spread throughout the brain and accumulated in areas of mbp expression. C,D: Transverse sections of olig1 and olig2 in situ hybridizations at the level of the fore-midbrain (C) and hindbrain (D). Red arrowheads indicate co-expression domains of olig1 and olig2.
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From the overlapping expression of olig1, olig2, and sox10, we conclude that oligodendrocytes originate in at least three distinct locations in zebrafish: medial in the midbrain, medial in the hindbrain, and ventral in the spinal cord. Upon differentiation, cells migrate away from these locations and to the prospective sites of myelination. Together, these results indicate that olig1 is expressed in differentiating oligodendrocytes prior to the expression of the late stage markers mbp and plp.