Migrating and myelinating potential of subventricular zone neural progenitor cells in white matter tracts of the adult rodent brain.

Adult neural stem cells in the subventricular zone (SVZ) produce neuronal progenitors that migrate along the rostral migratory stream (RMS) and generate olfactory interneurons. Here, we evaluate the migratory potential of SVZ cells outside the RMS and their capacity to generate oligodendrocytes in the adult brain. We show that SVZ cells migrate long distances when grafted into white matter tracts such as the cingulum (Ci) and corpus callosum (CC). Furthermore, 22 days postinjection, most present morphologic and phenotypic characteristics of cells committed to the oligodendrocyte lineage. Cells grafted in shiverer CC and Ci become MBP-positive oligodendrocytes, abundantly myelinating these white matter tracts. Type A progenitors are involved in this myelinating process. Altogether, this study reveals the migrating and myelinating potential of SVZ cells in a new environmental context. Therefore, SVZ cells stand as interesting candidates for the development of novel therapeutic strategies for demyelinating diseases.

Oligodendrocyte precursor cells generate pituicytes in vivo during neurohypophysis development.

In the vertebrate brain, much remains to be understood concerning the origin of glial cell diversity and the potential lineage relationships between the various types of glia. Besides astrocytes and myelin-forming oligodendrocytes, other macroglial cell populations are found in discrete areas of the central nervous system (CNS). They share functional features with astrocytes and oligodendrocytes but also display specific characteristics. Such specialized cells, called pituicytes, are located in the neurohypophysis (NH). Our work focuses on the lineage of the pituicytes during rodent development. First, we show that cells identified with a combination of oligodendrocyte precursor cell (OPC) markers are present in the developing rat NH. In culture, neonatal NH progenitors also share major functional characteristics with OPCs, being both migratory and bipotential, i.e. able to give rise to type 2 astrocytes and oligodendrocytes. We then observe that, either in vitro or after transplantation into myelin-deficient Shiverer brain, pieces of NH generate myelinating oligodendrocytes, confirming the oligodendrogenic potentiality of NH cells. However, no mature oligodendrocyte can be found in the NH. This led us to hypothesize that the OPCs present in the developing NH might be generating other glial cells, especially the pituicytes. Consistent with this hypothesis, the OPCs appear during NH development before pituicytes differentiate. Finally, we establish a lineage relationship between olig1+ cells, most likely OPCs, and the pituicytes by fate-mapping experiments using genetically engineered mice. This constitutes the first demonstration that OPCs generate glial cells other than oligodendrocytes in vivo.

Selection of poly-alpha 2,8-sialic acid mimotopes from a random phage peptide library and analysis of their bioactivity.

Poly-alpha 2-8 sialic acid (PSA), attached to the neural cell adhesion molecule, is a permissive determinant for numerous morphogenetic and neural plasticity processes, making it a potential therapeutic target. Here, using a monoclonal antibody specific for PSA, we screened a phage-display library and identified two cyclic nine-amino acid peptides (p1, p2) that are PSA epitope analogues. We evaluated their bioactivity in vitro and in vivo. In culture, micromolar concentrations of the peptides promoted axon growth, defasciculation, and migration of neural progenitors. When injected into developing chicken retina, the peptides modified the trajectory of retinal ganglion cell axons. Moreover, they enhanced migration of grafted neuroblasts in mouse brain. These effects were selective and dependent upon the presence of PSA on transplanted cells. Our results demonstrate the feasibility and therapeutic potential of enhancing PSA biological activity.