Myelinogenesis and Axonal Recognition by Oligodendrocytes in Brain Are Uncoupled inOlig1-Null Mice

Abstract

Myelin-forming oligodendrocytes facilitate saltatory nerve conduction and support neuronal functions in the mammalian CNS. Although the processes of oligodendrogliogenesis and differentiation from neural progenitor cells have come to light in recent years, the molecular mechanisms underlying oligodendrocyte myelinogenesis are poorly defined. Herein, we demonstrate the pivotal role of the basic helixloop-helix transcription factor, Olig1, in oligodendrocyte myelinogenesis in brain development. Mice lacking a functional Olig1 gene develop severe neurological deficits and die in the third postnatal week. In the brains of these mice, expression of myelin-specific genes is abolished, whereas the formation of oligodendrocyte progenitors is not affected. Furthermore, multilamellar wrapping of myelin membranes around axons does not occur, despite recognition and contact of axons by oligodendrocytes, and Olig1-null mice develop widespread progressive axonal degeneration and gliosis. In contrast, myelin sheaths are formed in the spinal cord, although the extent of myelination is severely reduced. At the molecular level, we find that Olig1 regulates transcription of the major myelin-specific genes, Mbp, Plp1, and Mag, and suppresses expression of a major astrocyte-specific gene, Gfap. Together, our data indicate that Olig1 is a central regulator of oligodendrocyte myelinogenesis in brain and that axonal recognition and myelination by oligodendrocytes are separable processes.

BMP signaling mutant mice exhibit glial cell maturation defects

“…Although this suggests that myelin protein expression is only delayed, it is possible that factors present in our culture system can override the block on myelin protein formation or that the in vitro milieu lacks inhibitory in vivo signals. In a recent study of Olig1-null mice, expression of myelin-forming genes was abolished in vivo, whereas expression of myelin proteins and elaboration of membrane sheets was present in vitro (Xin et al, 2005) indicating that expression of myelin proteins in vitro may not be the same as in vivo.…”

Identification of OLIG2 as the most specific glioblastoma stem cell marker starting from comparative analysis of data from similar DNA chip microarray platforms

“…At early embryonic stages, one key role of Olig2 is to maintain progenitor cells in a replication-competent state [67]. The structurally related Olig1 transcription factor is required for maturation of oligodendrocyte progenitors [68,69]. Although it is co-expressed with Olig2 at early stages, Olig1 function is dispensable for specification of neurons or oligodendrocytes from replication competent progenitor cells [62,66].…”

Promoting remyelination for the treatment of multiple sclerosis: opportunities and challenges

“…GPR17 is a Gi-coupled receptor with expression restricted to the early differentiation stages of oligodendrocyte-lineage cells, and it is downregulated during the peak period of myelination and in adulthood [29] . Gpr17-knockout mice show early-onset oligodendrocyte myelination, while Gpr17 overexpression inhibits oligodendrocyte differentiation and maturation both in vivo and in vitro [26] .…”