Data from: Loss of mTORC2 signaling in oligodendrocyte precursor cells delays myelination

Myelin abnormalities are increasingly being recognized as an important
component of a number of neurologic developmental disorders. The
integration of many signaling pathways and cell types are critical for
correct myelinogenesis. The PI3-K and mechanistic target of rapamycin
(mTOR) pathways have been found to play key roles. mTOR is found within
two distinct complexes, mTORC1 and mTORC2. mTORC1 activity has been shown
to play a major role during myelination, while the role of mTORC2 is not
yet well understood. To determine the role of mTORC2 signaling in
myelinogenesis, we generated a mouse lacking the critical mTORC2 component
Rictor in oligodendrocyte precursors (OPCs). Targeted deletion of Rictor
in these cells decreases and delays the expression of myelin related
proteins and reduces the size of cerebral white matter tracts. This is
developmentally manifest as a transient reduction in myelinated axon
density and g-ratio. OPC cell number is reduced at birth without
detectable change in proliferation with proportional reductions in mature
oligodendrocyte number at P15. The total number of oligodendrocytes as
well as extent of myelination, does improve over time. Adult conditional
knock-out (CKO) animals do not demonstrate a behavioral phenotype likely
due in part to preserved axonal conduction velocities. These data support
and extend prior studies demonstrating an important but transient
contribution of mTORC2 signaling to myelin development.