Figure 7. Antagonistic action of the EPAC inhibitor, ESI-09, on cAMP-induced SC differentiation and myelin sheath formation.

Differentiation (A-B) and myelination (C) assays were performed and analyzed essentially as described in previous figures. Cultures were incubated with the indicated concentrations (B) or 20 µM of ESI-09 (A, C) during the whole time course of the experiments, i.e. 3 days (A-B) and 10 days (C), respectively. ESI-09 prevented the expression of O1 (A-B) and the morphological transformation that occurs in response to cAMP (CPT-cAMP, 250 µM), as revealed by the phase contrast (PC) image shown in A (bottom panel). However, ESI-09 did not prevent the expression and nuclear localization of Krox-20 (A, middle panel, and B, right panel). In C, note the dramatic reduction in the number and distribution of O1 positive and MBP positive SCs in ESI-09-treated cultures.