DETERMINATION OF NEUROEPITHELIAL CELL FATE - INDUCTION OF THE OLIGODENDROCYTE LINEAGE BY VENTRAL MIDLINE CELLS AND SONIC HEDGEHOG

Near the floor plate of the embryonic neural tube there is a group of neuroepithelial precursor cells that are specialized for production of the oligodendrocyte lineage. We performed experiments to test whether specification of these neuroepithelial oligodendrocyte precursors, li ke other ventral neural cell types, depends on signals from the notoch ord and/or floor plate. We analyzed heterozygous Danforth's short tail (Sd/+) mutant mice, which lack a notochord and floor plate in caudal regions of the neural tube, and found that oligodendrocyte precursors did not appear at the ventricular surface where there was no floor pla te. Moreover, oligodendrocytes did not develop in explant cultures of Sd/+ spinal cord in the absence of a floor plate. When a second notoch ord was grafted into an ectopic position dorsolateral to the endogenou s notochord of a chicken embryo, an additional floor plate was induced along with an ectopic focus of oligodendrocyte precursors at the vent ricular surface. Oligodendrocytes developed in explants of intermediat e neural tube only when they were cocultured with fragments of notocho rd or in the presence of purified Sonic hedgehog (Shh) protein. Thus, signals from the notochord/floor plate, possibly involving Shh, are ne cessary and sufficient to induce the development of ventrally derived oligodendroglia. These signals appear to act by specifying the future fate(s) of neuroepithelial cells at the ventricular surface rather tha n by influencing the proliferation or differentiation of prespecified progenitor cells in the parenchyma of the cord. (C) 1996 Academic Pres s, Inc.