Figure 4.

MEK inhibition accelerates the development of CTIP2-competent progenitors and the pro-neural gene network

(A) Under Basal conditions, TBR1⁺ and CTIP2⁺ cells are present at D34, showing that progenitors can generate both layers. In contrast, eFGF2 treatment limits neurogenesis and only few TBR1⁺ neurons are born. After MEKi, CTIP2⁺ neurons predominate at the expense of TBR1. Inset shows magnified section.

(B–D) Quantification at D26 and D35 for TUJ1⁺ (B), TBR1⁺ (C), and CTIP2⁺ (D) neurons (n = 3–5 independent experiments, one-way ANOVA with Dunnett's correction).

(E) qRT-PCR at D26 showed increased CTIP2 and BRN2A mRNA after acute MEKi.

(F) BRN2⁺/SOX2⁺ progenitors were rare in eFGF2 conditions and increased following MEKi.

(G) The pro-neural genes FOXG1, PAX6, and ASCL1 were increased at D26 after MEKi, concomitant with increased CTIP2⁺ neurogenesis.

(H) eFGF2 induced AP-1 and c-MYC, downstream of FGFR activation.

(I) eFGF2 also increased levels of CCND1, required for G₁/S-phase transition (n = 3 independent experiments).

Data are mean ± SEM; ^∗p < 0.05, ^∗∗p < 0.01, ^∗∗∗p < 0.001, ^∗∗∗∗p < 0.0001. Scale bars, 200 μm (A) and 50 μm (F).