Cell-surface glycoprotein of oligodendrocyte progenitors involved in migration.

Myelination by oligodendrocytes in the CNS involves the migration to and recognition and ensheathment of axons. These distinct developmental phases of myelination are assumed to involve the interplay of a precisely regulated set of cell adhesion molecules expressed by both neurons and glial cells. These molecules remain largely unelucidated. In this paper we have identified a large (330 kDa) glycoprotein expressed by murine oligodendrocyte progenitor cells in vitro and in vivo that is downregulated as oligodendrocytes mature. Antigen-positive oligodendrocyte progenitor cells purified by panning develop into myelin-associated glycoprotein-positive oligodendrocytes and also adhere to cultured neurons. Polyclonal antibodies directed against the protein reduce the migration of oligodendrocyte progenitor cells. The observations suggest that the AN2 antigen may play a role in early stages of myelination.

AN2/NG2 protein-expressing glial progenitor cells in the murine CNS: isolation, differentiation, and association with radial glia.

During early neural development, the lineage specification of initially pluripotent progenitor cells is associated with proliferation, differentiation, and migration. Oligodendroglial progenitor cells migrate from their sites of origin to reach the axons that they will myelinate. We have described a cell-surface protein, AN2, expressed by oligodendroglial progenitor cells in vitro and showed that antibodies against AN2 inhibited the migration of cultured primary oligodendroglial progenitor cells, suggesting that the AN2 antigen plays a role in their migration. Recently, results from MALDI mass spectroscopy showed that AN2 is the mouse homologue of the rat NG2 protein. In this study, we have analyzed cells staining with AN2 antibodies during development and in the adult murine central nervous system (CNS), carried out double stainings with antibodies against NG2, and investigated the differentiation potential of cells in vitro after isolation from early postnatal brain using AN2 antibodies. AN2 and NG2 antibodies stained totally overlapping populations of cells in the CNS. AN2/NG2 expressing cells in embryonic and postnatal brain expressed the PDGF-alpha-receptor and in postnatal brain exhibited electrophysiological properties typical of glial progenitor cells. Cells isolated from early postnatal brain using AN2 monoclonal antibody developed into oligodendrocytes in low serum medium or into astrocytes in the presence of fetal calf serum. In the embryonic spinal cord, cells staining with AN2 antibodies were found closely apposed to radial glial cells, suggesting that glial precursors, like neurons, may use radial glia as scaffolds for migration.

Patients with active relapsing-remitting multiple sclerosis synthesize antibodies recognizing oligodendrocyte progenitor cell surface protein: implications for remyelination.

In multiple sclerosis (MS), remyelination of demyelinated lesions diminishes with disease progression for unknown reasons. Oligodendrocyte progenitor cells contribute to remyelination; however, antibodies specific for oligodendrocyte progenitor antigens could block remyelination by eliminating or impeding these cells. In myelinating cultures, cell lysis with antibody recognizing a progenitor cell-specific surface glycoprotein (AN2) suppressed the synthesis of myelin proteins. Cerebrospinal fluid from patients with relapsing-remitting active MS contains antibodies against AN2, whereas cerebrospinal fluid from patients with nonactive disease does not. This is the first report describing antibodies in MS against a progenitor cell-specific antigen that may contribute to the development and progression of chronically demyelinated lesions.