Spinal cord oligodendrocyte precursors arise in the ventral ventricular zone as a result of local signals. Ectopic oligodendrocyte precursors can be induced by sonic hedgehog (Shh) in explants of chick dorsal spinal

During development, the earliest cells of the oligodendrocyte lineage arise in the ventral ventricular zone of the spinal cord (Noll and Miller, 1993; Pringle and Richardson, 1993; Yu et al., 1994; Ono et al., 1995; Timsit et al., 1995). In the chick, oligodendrocyte precursors can be specifically identified beginning at around stage 29 (E6) by the monoclonal antibody (mAb) O4 (Ono et al., 1995, 1997a,b). These cells initially have a simple neuroepithelial morphology, and subsequently migrate dorsally and laterally to populate presumptive white matter (Ono et al., 1995). The origin of spinal cord oligodendrocyte precursors is influenced by local signals from the notochord, a mesodermal structure located ventral to the neural tube (Orentas and Miller, 1996; Pringle et al., 1996). For example, grafting an additional notochord dorsal to the spinal cord at stage 10 (E2) induces ectopic oligodendrocyte precursors adjacent to the transplanted notochord (Orentas and Miller, 1996; Pringle et al., 1996), and the addition of notochord to dorsal neural tube cultures results in the induction of oligodendrocytes (Trousse et al., 1995; Orentas and Miller, 1996; Pringle et al., 1996). The notochord is in fact required for the development of spinal cord oligodendrocytes. Inhibition of notochord development or ablation of the notochord early in development results in a failure of oligodendrocytes to appear in adjacent spinal cord (Pringle et al., 1996; Maier and Miller, 1997). The requirement for notochord is transient, since oligodendrocytes develop on a normal schedule in isolated cultures of spinal cord, separated from notochordal influences several days earlier (Warf et al., 1991). One candidate molecule for mediating the effects of the notochord on oligodendrocyte development is Sonic hedgehog. During normal development, the notochord contributes to the development of ventral spinal cord cell types in part by secretion of sonic hedgehog (Shh) (Echelard et al., 1993; Roelink et al., 1994, 1995). Sonic hedgehog induces floor plate, motor neurons and interneurons in a dose-dependent manner (Roelink et al., 1995; Ericson et al., 1997); relatively high concentrations induce floor plate and motor neurons while slightly lower concentrations induce motor neurons but not floor plate (Roelink et al., 1995; Ericson et al., 1997). Oligodendrocytes can be induced in dorsal spinal cord by similar concentrations of Shh to those required for motor neurons (Pringle et al., 1996) indicating that Shh is sufficient for the ectopic induction of spinal cord oligodendrocytes (Poncet et al., 1996; Pringle et al., 1996). The notochord is not the only ventrally located source of Shh. The floor plate (Echelard et al., 1993; Roelink et al., 1994, 1995; Marti et al., 1995), and to a lesser extent motor neurons (Bitgood and McMahon, 1996), also produce Shh during specific stages of development. The demonstration that similar concentrations of Shh induced 2419 Development 126, 2419-2429 (1999) Printed in Great Britain © The Company of Biologists Limited 1999 DEV1420