The effects of Epac2 modulation on cortical neurite outgrowth.
(A–C) Epac2 agonist S-220 promoted significant neurite outgrowth. (A) Control. (B) Treated with S-220. (C) Quantification of total neurite length shows that S-220-treated neurons had significantly longer neurites. (D–F) Epac2 antagonist ESI-05 significantly decreased cortical neurite outgrowth. (D) Control. (E) Treated with ESI-05. (F) Quantification of total neurite length shows that ESI-05-treated neurons had significantly shorter neurites. (G–I) siRNA knockdown of Epac2 significantly decreased cortical neurite outgrowth. G, Scrambled siRNA control. (H) Epac2 siRNA-treated. (I) Quantification of total neurite length shows that Epac2 siRNA-treated neurons had significantly shorter neurites. A, B, D, E, Cultures were grown for 24 hours. G, H, Cultures were grown for 48 hours. All cultures were stained for β-tubulin-III. *P < 0.05, ***P < 0.001. n = 3/group. Scale bars: A–E, 50 µm; G and H, 100 µm. Adapted from Guijarro-Belmar et al. (2019).