Deciphering the Oligodendrogenic Program of Neural Progenitors: Cell Intrinsic and Extrinsic Regulators

In the developing and adult CNS, neural stem/progenitor cells (NSPCs) and oligodendroglial progenitor cells (OPCs) follow an oligodendrogenic process with the aim of myelinating axons. This process is to a high degree regulated by an oligodendrogenic program (OPr) composed of intrinsic and extrinsic factors that modulate the different steps required for NSPCs to differentiate into myelinating oligodendrocytes. Even though NSPCs and OPCs are present in the diseased CNS and have the capacity to generate oligodendrocytes, sparse remyelination of axons constitutes a major constraint in therapies toward multiple sclerosis (MS) and spinal cord injury (SCI). Lack of pro-oligodendrogenic factors and presence of anti-oligodendrogenic activities are thought to be the main reasons for this limitation. Thus, molecular and cellular strategies aiming at remyelination and at targeting such pro- and anti-oligodendrogenic mechanisms are currently under investigation. The present review summarizes the current knowledge on the OPr; it implements our own findings on mesenchymal stem cell-derived pro-oligodendroglial factors and on the role of p57/kip2 in oligodendroglial differentiation. Moreover, it describes molecular and cellular approaches for the development of future therapies toward remyelination.