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Parkinson's disease symptoms can be improved by transplanting fetal dopamine cells into the putamen of parkinsonian patients. Because the supply of human donor tissue is limited and variable, an alternative and genetically modifiable non-human source of tissue would be valuable. We have generated cloned transgenic bovine embryos, 42% of which developed beyond 40 days. Dopamine cells collected from the ventral mesencephalon of the cloned fetuses 42 to 50 days post-conception survived transplantation into immunosuppressed parkinsonian rats and cells from cloned and wild-type embryos improved motor performance. Somatic cell cloning can efficiently produce transgenic animal tissue for treating parkinsonism.

XlPOU 2, a member of the class III POU domain family, is expressed initially in Spemann’s organizer, and later, in discrete regions of the developing nervous system in Xenopus laevis. XlPOU 2 may act downstream from initial neural induction events, since it is activated by the neural inducer, noggin. To determine if XlPOU 2 participates in the early events of neurogenesis, synthetic mRNA was microinjected into specific blastomeres of the 32-cell stage embryo. Misexpression of XlPOU 2 in the epidermis causes a direct switch in cell fate from an epidermal to a neuronal phenotype. In the absence of mesoderm induction, XlPOU 2 has the ability to induce a neuronal phenotype in uncommitted ectoderm. These data demonstrate the potential of XlPOU 2 to act as a master regulator of neurogenesis.

XlPOU 2, a member of the class III POU-domain family, is expressed initially at mid-blastula transition (MBT) and during gastrulation in the entire marginal zone mesoderm, including Spemann’s Organizer (the Organizer). To identify potential targets of XlPOU 2, the interaction of XlPOU 2 with other genes co-expressed in the Organizer was examined by microinjecting XlPOU 2’s mRNA into the lineage of cells that contributes to the Organizer, head mes-enchyme and prechordal plate. XlPOU 2 suppresses the expression of a number of dorsal mesoderm-specific genes, including gsc, Xlim-1, Xotx2, noggin and chordin, but not Xnot. As a consequence of the suppression of dorsal mesoderm gene expression, bone morphogenetic factor-4 (Bmp-4), a potent inducer of ventral mesoderm, is activated in the Organizer. Gsc is a potential target of XlPOU 2. XlPOU 2 is capable of binding a class III POU protein binding site (CATTAAT) that is located within the gsc promoter, in the activin-inducible (distal) element. Furthermore, XlPOU 2 suppresses the activation of the gsc promoter by activin signaling. At the neurula and tailbud stages, dorsoanterior structures are affected: embryos displayed micropthalmia and the loss of the first branchial arch, as detected by the expression of pax-6, Xotx2 and en-2. By examining events downstream from the Wnt and chordin pathways, we determined that XlPOU 2, when overexpressed, acts specifically in the Organizer, downstream from GSK-3β of the Wnt pathway and upstream from chordin. The interference in dorsalizing events caused by XlPOU 2 was rescued by chordin. Thus, in addition to its direct neuralizing ability, in a different context, XlPOU 2 has the potential to antagonize dorsalizing events in the Organizer.