Figure 7.

Overexpression of activated β-catenin in oligodendrocyte lineage cells during remyelination in the adult causes a delay in repair due to a delay in OLP differentiation, without affecting their recruitment into the lesion. (A) Similar numbers of OLPs expressing Nkx2.2 protein, are present within remyelinating adult spinal cord lesions at 10 dpl in wild type (WT), Olig2cre control, and Olig2cre/DA-Cat mice, and also at 5 dpl and 14 dpl in wild type (gray bars), Olig2cre control (white bars), andOlig2cre/DA-Cat mice (black bars). (B) There is a significant reduction [(*) P = 0.028 at 10 dpl; (**) P = 0.0009 at 14 dpl] in the subsequent differentiation of recruited OLPs into mature remyelinating oligodendrocytes expressing PLP message during remyelination in the Olig2cre/DA-Cat (black bars) compared with wild type (gray bars) or Olig2cre controls (white bars). (C) Delay in OLP differentiation during remyelination results in thinner myelin sheaths at 14 dpl in Olig2cre/DA-Cat mice evident by EM, and with significant (P = 4.6 × 10⁻⁹) change in G-ratio. (D) APCmin mice, lacking one allele of the Wnt pathway inhibitor APC, show a marked deficit in remyelination of adult spinal cord at 14 dpl, due to a significant reduction [(*) P = 0.012] of differentiation into mature PLP-expressing oligodendrocytes, despite normal recruitment of Nkx2.2-expressing OLPs.